心肌梗死 炎症介质 1466 - 1861 0962 - 9351 Hindawi 10.1155 / 2018/8430614 8430614 研究文章 饮食n PUFA可能减弱实验性结肠炎 贝纳 Cloe 1 2 罗纳德。 3 Salameh 埃米琳 1 Mbodji Khaly 1 上野 Aito 3 4 Coeffier 莫伊兹 1 5 吉林 Charlene 1 http://orcid.org/0000 - 0002 - 1713 - 7797 戈什 Subrata 3 6 Savoye Guillaume 1 2 Marion-Letellier 瑞秋 1 Sung-Ling 1 INSERM UMR 1073 在这里de Medecine-Pharmacie 22大道Gambetta 76183年鲁昂Cedex 法国 2 美国胃肠病学 鲁昂大学医院 1街Germont 76031年鲁昂Cedex 法国 univ-rouen.fr 3 卡尔加里大学 肠胃研究小组 斯奈德慢性疾病研究所 卡尔加里 AB 加拿大 ucalgary.ca 4 先进的IBD研究和治疗中心 北里研究所医院 东京 日本 kitasato-u.ac.jp 5 营养单位 鲁昂大学医院 1街Germont 76031年鲁昂Cedex 法国 univ-rouen.fr 6 转化医学研究所 伯明翰大学 伯明翰 英国 birmingham.ac.uk 2018年 15 2 2018年 2018年 28 07年 2017年 13 10 2017年 31日 10 2017年 15 2 2018年 2018年 版权©2018 Cloe贝等。 这是一个开放的文章在知识共享归属许可下发布的,它允许无限制的使用,分布和繁殖在任何媒介,提供最初的工作是正确的引用。

背景。炎症性肠病(IBD)发生在遗传易感性的人暴露于环境诱因。饮食一直被怀疑为炎症性肠病的发展作出贡献。补充与n - 3多不饱和脂肪酸(PUFA)防止肠道炎症在啮齿动物模型在临床试验显示没有好处。我们假设干预时机是至关重要的和膳食脂肪酸模式可能会影响肠道环境修改炎症创世纪。本研究的目的是评估膳食PUFA成分对肠道炎症的影响。 方法。动物收到饮食不同在PUFA组成四个星期之前TNBS-induced结肠炎。结肠炎症标记物和肠道屏障功能参数进行评估。炎症通路PCR确定数组。 结果。n - 3饮食显著减少结肠伊诺,cox - 2表达,il - 6生产、LTB4生产,但倾向于降低结肠肿瘤坏死因子 α生产( P = 0.0617 )相比,控制饮食。紧密连接蛋白(claudin-1 occludin)表达式和MUC2和TFF3 mRNA水平组之间没有不同。涂有n - 9的饮食也减少了结肠il - 6生产( P < 0.05 )。 结论。饮食影响n - 3 PUFA结肠炎发展衰减炎症标记物。进一步的研究需要更好地与一个科学原理定义饮食建议。 1。介绍<gydF4y2Ba/title> <p>炎症性肠病(IBD)影响遗传倾向的人暴露于环境诱因(<gydF4y2Baxref ref-type="bibr" rid="B1"> 1<gydF4y2Ba/xref>]。在环境因素中,饮食习惯一直被怀疑为炎症性肠病的发展(<gydF4y2Baxref ref-type="bibr" rid="B2"> 2<gydF4y2Ba/xref>]。IBD患者通常被认为是饮食作为一个潜在的触发启动疾病或导致复发(<gydF4y2Baxref ref-type="bibr" rid="B3"> 3<gydF4y2Ba/xref>],这个概念导致排除饮食特别是儿童(<gydF4y2Baxref ref-type="bibr" rid="B4"> 4<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>IBD的发病率增加与高动物蛋白的饮食有关。事实上,饮食模式之间的联系(脂肪或蛋白质)和克罗恩病(CD)的风险是来自日本的一项研究中发现<gydF4y2Baxref ref-type="bibr" rid="B5"> 5<gydF4y2Ba/xref>而增加消费的动物蛋白与更高的IBD风险研究中有关从法国<gydF4y2Baxref ref-type="bibr" rid="B6"> 6<gydF4y2Ba/xref>]。系统回顾表明,西方饮食模式(高脂肪、高n-6多不饱和脂肪酸(PUFA)和高肉)是与炎症性肠病的风险增加有关<gydF4y2Baxref ref-type="bibr" rid="B7"> 7<gydF4y2Ba/xref>]。最近,一项研究在103年进行IBD患者用食物频率问卷1年多,作者发现积极联系肉类摄取量和疾病复发(<gydF4y2Baxref ref-type="bibr" rid="B8"> 8<gydF4y2Ba/xref>]。同样,西方饮食有害影响肠道屏障功能和生态失调在炎症性肠病小鼠模型(<gydF4y2Baxref ref-type="bibr" rid="B9"> 9<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>尽管n - 3和n-6 PUFA在人类营养是必不可少的,西方饮食的特点是一个不平衡的比例这两种类型的PUFA (n - 3 / n-6比率)。的确,亚油酸(洛杉矶,n-6 PUFA)消费显著增加(整个20世纪的三倍)<gydF4y2Baxref ref-type="bibr" rid="B10"> 10<gydF4y2Ba/xref>]。许多流行病学研究强调饮食摄入量的单不饱和脂肪酸的作用(MUFA)或PUFA在溃疡性结肠炎(UC)的发展。摄入较多的LA与风险增加有关加州大学(<gydF4y2Baxref ref-type="bibr" rid="B11"> 11<gydF4y2Ba/xref>),二十二碳六烯酸(DHA) (n - 3 PUFA) [<gydF4y2Baxref ref-type="bibr" rid="B12"> 12<gydF4y2Ba/xref>)或油酸(n - 9 MUFA) [<gydF4y2Baxref ref-type="bibr" rid="B13"> 13<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B14"> 14<gydF4y2Ba/xref>]消费是有益的。Ananthakrishnan等<gydF4y2Baitalic> 。<gydF4y2Ba/italic>发现更大的鱼的摄入量与风险有关的CD (<gydF4y2Baxref ref-type="bibr" rid="B15"> 15<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>我们和其他人证明抗炎效果的n - 3多不饱和脂肪酸在啮齿动物炎症性肠病模型(<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B21"> 21<gydF4y2Ba/xref>)在临床试验失败(<gydF4y2Baxref ref-type="bibr" rid="B22"> 22<gydF4y2Ba/xref>]。我们假设干预时机是至关重要的和膳食脂肪酸模式可能会影响肠道环境修改炎症《创世纪》(<gydF4y2Baxref ref-type="bibr" rid="B23"> 23<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>这项研究的目的是探讨膳食脂肪酸组成的影响在肠道炎症的发病之前管理2,4,6-trinitrobenzene磺酸(TNBS)。为此,老鼠再辅以饮食不同n - 3 / n-6 / n - 9比复制从务实的西方饮食饮食模式。<gydF4y2Ba/p> </sec> <sec id="sec2"> <title>2。材料和方法<gydF4y2Ba/title> <sec id="sec2.1"> <title>2.1。动物和研究设计<gydF4y2Ba/title> <p>年轻Sprague-Dawley雄性老鼠重75 - 100克从Janvier购买(Le Genest圣岛,法国)和允许访问食物和水随意。1星期后适应环境,50大鼠随机分为实验组5;美联储控制(CTRL)组与控制饮食和收到车辆,而colitic团体包括TNBS, n - 3, n-6,和n - 9组与控制饮食喂养,n - 3饮食,n-6饮食,饮食和n - 9,分别收到TNBS结肠炎感应。体重每天都在研究变化进行了监测。实验饮食后4周(28天1),24小时接受食物的老鼠剥夺TNBS前或车辆管理。在结肠炎感应(0到2天),老鼠提供控制饮食。实验设计如图的概述<gydF4y2Baxref rid="fig1a" ref-type="fig"> 1(一)<gydF4y2Ba/xref>。<gydF4y2Ba/p> <fig-group id="fig1"> <label>图1<gydF4y2Ba/label> <p>对老鼠的实验设计和临床参数接收不同在他们的饮食不饱和脂肪酸成分TNBS-induced结肠炎紧随其后。(一)实验设计。老鼠接受饮食不同在PUFA组成四个星期之前结肠炎在第0天感应。老鼠在第二天被杀。在第二天(b)体重。(c)体重后续从28天到第二天。<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>与所有结肠炎组(n-6 TNBS, n, n - 9)。<gydF4y2Ba/p> <fig id="fig1a"> <label>(一)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.001a"></graphic> </fig> <fig id="fig1b"> <label>(b)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.001b"></graphic> </fig> <fig id="fig1c"> <label>(c)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.001c"></graphic> </fig> </fig-group> <p>所有动物处理和治疗程序进行按照两个法国国家规定和欧盟条例(358年欧洲共同体官方杂志L 18/12/1986)和RML是由法国政府授权使用这种动物协议(授权n 76 - 106°)。<gydF4y2Ba/p> </sec> <sec id="sec2.2"> <title>2.2。饮食<gydF4y2Ba/title> <p>四种等热量的饮食和isolipidic实验准备和几个脂肪酸比例:<gydF4y2Balist> <list-item> <label>(我)<gydF4y2Ba/label> </list-item> </list></p> <p>匹配的正常饮食均衡的饮食和n - 3 / n-6 / n - 9比率等于1:4:16作为脂肪比例推荐的膳食指南和文献中描述为一个均衡的饮食<gydF4y2Baxref ref-type="bibr" rid="B24"> 24<gydF4y2Ba/xref>]。控制饮食是CTRL和TNBS组。推荐的膳食n-6 / n比率大约是4在人类营养与饮食控制在这个研究。<gydF4y2Ba/p> <list-item> <label>(2)<gydF4y2Ba/label> <p>n - 3饮食有一个n - 3 / n-6 / n - 9比率等于1:1:4。我们选择一个n - 3 / n-6比率等于1:1因为这个比例是饮食建议的目标在日本IBD患者临床试验(<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>]。此外,n - 3 / n-6比率通常被用于实验研究调查的影响[n - 3治疗<gydF4y2Baxref ref-type="bibr" rid="B24"> 24<gydF4y2Ba/xref>]。<gydF4y2Ba/p> </list-item> <list-item> <label>(3)<gydF4y2Ba/label> <p>n-6饮食上西方饮食与n - 3 / n-6 / n - 9比1:16:16。饮食n-6 / n比率是人类西方饮食(约15<gydF4y2Baxref ref-type="bibr" rid="B26"> 26<gydF4y2Ba/xref>),这个比例是有用的突出特征的西方饮食的不平衡。<gydF4y2Ba/p> </list-item> <list-item> <label>(iv)<gydF4y2Ba/label> <p>涂有n - 9的饮食也有类似的n - 3 / n-6比CTRL饮食但富含n - 9 MUFA。这个n / n - 9比率等于1:24与观察到人们遵循地中海饮食(比<gydF4y2Baxref ref-type="bibr" rid="B26"> 26<gydF4y2Ba/xref>]。<gydF4y2Ba/p> </list-item> <p></p> <p>详细的饮食成分如表所示<gydF4y2Baxref rid="tab1" ref-type="table"> 1<gydF4y2Ba/xref>。<gydF4y2Ba/p> <table-wrap id="tab1"> <label>表1<gydF4y2Ba/label> <p>脂肪酸的合成实验饮食。<gydF4y2Ba/p> <table> <thead> <tr> <th></th> <th align="center">CTRL<gydF4y2Ba/th> <th align="center">n - 3饮食<gydF4y2Ba/th> <th align="center">n-6饮食<gydF4y2Ba/th> <th align="center">涂有n - 9的饮食<gydF4y2Ba/th> </tr> </thead> <tbody> <tr> <td align="left">饮食的脂肪(克/ 1000克)<gydF4y2Ba/td> <td align="center">49.7<gydF4y2Ba/td> <td align="center">49.4<gydF4y2Ba/td> <td align="center">49.7<gydF4y2Ba/td> <td align="center">49.8<gydF4y2Ba/td> </tr> <tr> <td align="left">饱和脂肪(g)<gydF4y2Ba/td> <td align="center">10.2<gydF4y2Ba/td> <td align="center">9.9<gydF4y2Ba/td> <td align="center">9.3<gydF4y2Ba/td> <td align="center">9.6<gydF4y2Ba/td> </tr> <tr> <td align="left">MUFA (g)<gydF4y2Ba/td> <td align="center">29.8<gydF4y2Ba/td> <td align="center">26.2<gydF4y2Ba/td> <td align="center">20.1<gydF4y2Ba/td> <td align="center">32.8<gydF4y2Ba/td> </tr> <tr> <td align="left">PUFA (g)<gydF4y2Ba/td> <td align="center">9.8<gydF4y2Ba/td> <td align="center">13.3<gydF4y2Ba/td> <td align="center">20.3<gydF4y2Ba/td> <td align="center">7.4<gydF4y2Ba/td> </tr> <tr> <td align="left">n-6脂肪酸(g)<gydF4y2Ba/td> <td align="center">7.9<gydF4y2Ba/td> <td align="center">7.3<gydF4y2Ba/td> <td align="center">19.1<gydF4y2Ba/td> <td align="center">6.1<gydF4y2Ba/td> </tr> <tr> <td align="left">n - 3脂肪酸(g)<gydF4y2Ba/td> <td align="center">1。8<gydF4y2Ba/td> <td align="center">6.1<gydF4y2Ba/td> <td align="center">1。2<gydF4y2Ba/td> <td align="center">1。3<gydF4y2Ba/td> </tr> <tr> <td align="left">n - 9脂肪酸(g)<gydF4y2Ba/td> <td align="center">29.3<gydF4y2Ba/td> <td align="center">25.8<gydF4y2Ba/td> <td align="center">19.8<gydF4y2Ba/td> <td align="center">32.2<gydF4y2Ba/td> </tr> <tr> <td align="left">n - 3 / n-6 / n - 9比率<gydF4y2Ba/td> <td align="center">1:16<gydF4y2Ba/td> <td align="center">1:1:4<gydF4y2Ba/td> <td align="center">1:十六16<gydF4y2Ba/td> <td align="center">1:4:24<gydF4y2Ba/td> </tr> </tbody> </table> </table-wrap> </sec> <sec id="sec2.3"> <title>2.3。感应的结肠炎<gydF4y2Ba/title> <p>管理TNBS (Sigma-Aldrich公司Saint-Quentin-Fallavier法国)是用于结肠炎感应如前所述<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>n-6 TNBS, n, n - 9组(colitic组)。使用麻醉老鼠牺牲试剂(氯胺酮和甲苯噻嗪)在第二天进行进一步的分析。<gydF4y2Ba/p> </sec> <sec id="sec2.4"> <title>2.4。免疫印迹<gydF4y2Ba/title> <p>PBS、蛋白酶抑制剂的鸡尾酒和磷酸酶抑制剂鸡尾酒买来Sigma-Aldrich (Saint-Quentin-Fallavier、法国)。4 - 12% NuPAGE凝胶和SeeBlue五彩缤纷的标准从英杰公司(法国- pontoise)。冷冻结肠癌样本均质在PBS 0.1%蛋白酶抑制剂鸡尾酒和1%磷酸酶抑制剂。匀浆离心机(12000<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"> <mml:mi> g<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>15分钟4°C)和上层的收集。蛋白质浓度测定在布拉德福德的比色方法。整除的上层清液含有等量的蛋白质(30<gydF4y2Baitalic> μ<gydF4y2Ba/italic>g)在4 - 12% NuPAGE分离,然后转移到硝酸纤维素(Hybond,通用电气医疗集团,英国)。鼠标单克隆抗体anti-PPAR<gydF4y2Baitalic> γ<gydF4y2Ba/italic>(sc - 7273),山羊多克隆anti-COX-2 (sc - 1747),鼠标anti-iNOS (sc - 7271),兔多克隆anti-HNF-4 (sc - 8987),和HRP-conjugated二级抗体来自圣克鲁斯生物技术(Le Perray-en-Yvelines Tebu,法国)。兔子anti-claudin-1和鼠标anti-occludin,分别从生活中获得技术和表达载体。阻塞后,膜被孵化与特定主要抗体的稀释1:100(间接宾语),1:500 (HNF-4, cox - 2和PPAR<gydF4y2Baitalic> γ<gydF4y2Ba/italic>),1:1000 (claudin-1 occludin。三洗后,膜被孵化与二级HRP-linked抗体免疫球蛋白(cox - 2), anti-rabbit免疫球蛋白(HNF-4 claudin-1)和anti-mouse免疫球蛋白(进气阀打开,PPAR<gydF4y2Baitalic> γ<gydF4y2Ba/italic>和occludin)抗体。增强化学发光测光工具包(美国通用电气医疗集团)是用于immunodetection。光密度测量的数据归一化后的管家蛋白(<gydF4y2Baitalic> β<gydF4y2Ba/italic>肌动蛋白)科学成像系统(图像QuantTL,通用电气医疗集团)。<gydF4y2Ba/p> </sec> <sec id="sec2.5"> <title>2.5。RNA分离和基因表达分析<gydF4y2Ba/title> <p>结肠样品在液氮冷冻和储存在−RNA制备前80°C。总RNA分离大鼠结肠标本使用商业RNA净化设备(SV总RNA隔离设备,Promega,麦迪逊,WI)和Muc2的mRNA表达(引物序列F: CCTTGCTCTGCCATACCCGT R: ACACTGGTCCTCTCCTCCCT)和TFF-3 (F: TAACCCTGCTGCTGGTCCTG R: GTTTGAAGCACCAGGGCACA)和内部控制(GAPDH)测量中存在。此外,toll样受体信号通路中的基因表达测定实时PCR阵列根据制造商的协议(pamm - 0018 zd SA生物科学,弗雷德里克,MD)在CFX96 thermocycler (Bio-Rad大力神,CA)。数据表达在褶皱的监管。褶皱的变化(折叠的区别)由方程计算2 (−∆∆CT)。褶皱的规定,软件转换褶皱变化值小于1(即基因表达下调)通过返回负倒数。<gydF4y2Ba/p> </sec> <sec id="sec2.6"> <title>2.6。结肠细胞因子和LTB4生产<gydF4y2Ba/title> <p>肿瘤坏死因子的浓度<gydF4y2Baitalic> α<gydF4y2Ba/italic>,il - 1<gydF4y2Baitalic> β<gydF4y2Ba/italic>,在结肠LTB4匀浆是由ELISA检测(研发系统、里尔、法国)遵循制造商的指示。<gydF4y2Ba/p> </sec> <sec id="sec2.7"> <title>2.7。蛋白水解途径活动<gydF4y2Ba/title> <p>蛋白水解的评估活动(caspase-like和chymotrypsin-like)是由spectrofluorometric微量滴定板荧光计(贝特密特拉神940磅,技术)使用fluorogenic蛋白酶体基质存在与否的特定的蛋白酶体抑制剂如前所述[<gydF4y2Baxref ref-type="bibr" rid="B27"> 27<gydF4y2Ba/xref>]。<gydF4y2Ba/p> </sec> <sec id="sec2.8"> <title>2.8。统计分析<gydF4y2Ba/title> <p>进行了统计比较使用GraphPadPrism 5。数据表示为±SEM。体重变化和食物摄入量与双向方差分析分析重复测量图基的事后测试。所有其他的变量进行了分析通过单向方差分析Bonferroni事后测试或克鲁斯卡尔-沃利斯检验。差异被认为是重要的<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>。<gydF4y2Ba/p> </sec> </sec> <sec id="sec3"> <title>3所示。结果<gydF4y2Ba/title> <sec id="sec3.1"> <title>3.1。TNBS-Induced结肠炎减少体重<gydF4y2Ba/title> <p>Colitic组较低体重相比,控制大鼠(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)第二天但是没有colitic组之间的差异(图<gydF4y2Baxref rid="fig1b" ref-type="fig"> 1 (b)<gydF4y2Ba/xref>)。<gydF4y2Ba/p> </sec> <sec id="sec3.2"> <title>3.2。TNBS-Induced结肠炎炎症标记物增加<gydF4y2Ba/title> <p>结肠体重/长度比率增加colitic老鼠相比,对照组(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>对TNBS和n - 3,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>n-6和n - 9,图<gydF4y2Baxref rid="fig2a" ref-type="fig"> 2(一个)<gydF4y2Ba/xref>colitic人群(图)没有显著差异<gydF4y2Baxref rid="fig2a" ref-type="fig"> 2(一个)<gydF4y2Ba/xref>)。结肠伊诺colitic组显著高于对照组(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.0141<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,图<gydF4y2Baxref rid="fig2b" ref-type="fig"> 2 (b)<gydF4y2Ba/xref>)。<gydF4y2Ba/p> <fig-group id="fig2"> <label>图2<gydF4y2Ba/label> <p>炎症标记物的老鼠接受饮食不同在不饱和脂肪酸组成4周TNBS-induced结肠炎紧随其后。(一)结肠/重量长度在第二天。(b)结肠伊诺表达式代表凝胶在第二天。(c)结肠il - 6和TNF (d)<gydF4y2Baitalic> α<gydF4y2Ba/italic>生产。5-Aminosalicylic酸(5-ASA)使用积极的抗炎控制。数据从colitic老鼠相比,1路的方差分析其次是图基期末测验。<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M11"> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M12"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>与CTRL,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M13"> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M14"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>与CTRL,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M15"> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M16"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>对TNBS。<gydF4y2Ba/p> <fig id="fig2a"> <label>(一)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.002a"></graphic> </fig> <fig id="fig2b"> <label>(b)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.002b"></graphic> </fig> <fig id="fig2c"> <label>(c)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.002c"></graphic> </fig> <fig id="fig2d"> <label>(d)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.002d"></graphic> </fig> </fig-group> </sec> <sec id="sec3.3"> <title>3.3。n - 3饮食减少结肠炎症标记物<gydF4y2Ba/title> <p>在结肠炎组,n - 3组较低相比,结肠伊诺TNBS集团(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M17"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,图<gydF4y2Baxref rid="fig2b" ref-type="fig"> 2 (b)<gydF4y2Ba/xref>)。结肠il - 6生产在n - 3和n-6组相比显著降低TNBS集团(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M18"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>同时,图<gydF4y2Baxref rid="fig2c" ref-type="fig"> 2 (c)<gydF4y2Ba/xref>),结肠肿瘤坏死因子<gydF4y2Baitalic> α<gydF4y2Ba/italic>结肠炎团体间的产量没有显著差异(图<gydF4y2Baxref rid="fig2d" ref-type="fig"> 2 (d)<gydF4y2Ba/xref>),但倾向于降低n组相比TNBS组(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M19"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.0617<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。转录因子HNF-4<gydF4y2Baitalic> α<gydF4y2Ba/italic>和PPAR<gydF4y2Baitalic> γ<gydF4y2Ba/italic>表情没有不同组间(数据没有显示)。<gydF4y2Ba/p> </sec> <sec id="sec3.4"> <title>3.4。n - 3饮食降低cox - 2表达和LTB4生产在结肠<gydF4y2Ba/title> <p>在结肠炎组,n - 3组较低结肠cox - 2表达相比TNBS集团(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M20"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,图<gydF4y2Baxref rid="fig3a" ref-type="fig"> 3(一个)<gydF4y2Ba/xref>)。此外,结肠LTB4生产低n组相比TNBS集团(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M21"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,图<gydF4y2Baxref rid="fig3b" ref-type="fig"> 3 (b)<gydF4y2Ba/xref>)。<gydF4y2Ba/p> <fig-group id="fig3"> <label>图3<gydF4y2Ba/label> <p>类二十烷酸在大鼠不同途径的不饱和脂肪酸组成4周TNBS-induced结肠炎紧随其后。(一)结肠cyclooxygenase-2代表凝胶(cox - 2)表达和(b)结肠LTB4生产在第二天。5-Aminosalicylic酸(5-ASA)使用积极的抗炎控制。数据从colitic老鼠相比,1路的方差分析其次是图基期末测验。<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M22"> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M23"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>对TNBS,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M24"> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M25"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>对TNBS,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M26"> <mml:mtext> 美元<gydF4y2Ba/mml:mtext> </mml:math> </inline-formula>意味着<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M27"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>对n - 3。<gydF4y2Ba/p> <fig id="fig3a"> <label>(一)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.003a"></graphic> </fig> <fig id="fig3b"> <label>(b)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.003b"></graphic> </fig> </fig-group> <sec id="sec3.4.1"> <title>3.4.1。肠道屏障功能不受饮食治疗<gydF4y2Ba/title> <p>紧密连接蛋白claudin-1和occludin没有不同组间(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M28"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.4750<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>和<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M29"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.8553<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,分别地。,Figures<xref ref-type="fig" rid="fig4a"> 4(一)<gydF4y2Ba/xref>和<gydF4y2Baxref ref-type="fig" rid="fig4b"> 4 (b)<gydF4y2Ba/xref>)。TFF3 mRNA水平没有不同组间(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M30"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.3729<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,图<gydF4y2Baxref ref-type="fig" rid="fig4c"> 4 (c)<gydF4y2Ba/xref>)。MUC2 mRNA水平没有不同组间(1路的方差分析,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M31"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.0381<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,后续测试<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M32"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,图<gydF4y2Baxref ref-type="fig" rid="fig4"> 4 (d)<gydF4y2Ba/xref>)。<gydF4y2Ba/p> <fig-group id="fig4"> <label>图4<gydF4y2Ba/label> <p>肠道屏障参数老鼠接受饮食不同在不饱和脂肪酸组成4周TNBS-induced结肠炎紧随其后。(a)结肠claudin-1表达式,(b) occludin的表情,(c)三叶草因子3 (TFF3) mRNA水平,并在第二天(d) MUC2 mRNA水平。(e)代表凝胶结肠claudin-1和occludin的表达式。5-Aminosalicylic酸(5-ASA)使用积极的抗炎控制。数据从colitic老鼠相比,1路的方差分析其次是图基期末测验。<gydF4y2Ba/p> <fig id="fig4a"> <label>(一)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.004a"></graphic> </fig> <fig id="fig4b"> <label>(b)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.004b"></graphic> </fig> <fig id="fig4c"> <label>(c)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.004c"></graphic> </fig> <fig id="fig4d"> <label>(d)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.004d"></graphic> </fig> <fig id="fig4e"> <label>(e)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/mi/2018/8430614.fig.004e"></graphic> </fig> </fig-group> </sec> </sec> <sec id="sec3.5"> <title>3.5。结肠炎或饮食PUFA没有修改蛋白酶体活动<gydF4y2Ba/title> <p>胰凝乳蛋白酶和trypsin-like活动没有不同colitic人群(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M33"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.3510<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>和<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M34"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.0651<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,分别地。,data not shown).</p> </sec> <sec id="sec3.6"> <title>3.6。饮食调制的炎症基因的表达<gydF4y2Ba/title> <p>结肠炎组,n - 3饮食调节IL-1A, TLR-2和MA2K3基因,而n - 9饮食调节地基因(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M35"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.044<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M36"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.013<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M37"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.021<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,分别地。、表<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。n-6调节HMGB1 (<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M38"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.042<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)而不影响TLR通路(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M39"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>、表<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。<gydF4y2Ba/p> <table-wrap id="tab2"> <label>表2<gydF4y2Ba/label> <p>炎症通路PCR数组的老鼠接受饮食不同的不饱和脂肪酸成分TNBS-induced结肠炎紧随其后。从大鼠结肠RNA接受饮食不同在他们的不饱和脂肪酸成分TNBS-induced结肠炎的发病。结果相比,老鼠接受TNBS控制饮食。数据以粗体TNBS老鼠显著不同。<gydF4y2Ba/p> <table> <thead> <tr> <th align="left" rowspan="2"></th> <th align="center" colspan="2">n - 3饮食<gydF4y2Ba/th> <th align="center" colspan="2">n-6饮食<gydF4y2Ba/th> <th align="center" colspan="2">涂有n - 9的饮食<gydF4y2Ba/th> </tr> <tr> <th align="center">褶皱监管<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M40"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>价值<gydF4y2Ba/th> <th align="center">褶皱监管<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M41"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>价值<gydF4y2Ba/th> <th align="center">褶皱监管<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M42"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>价值<gydF4y2Ba/th> </tr> </thead> <tbody> <tr> <td align="left">Il1a<gydF4y2Ba/td> <td align="center"> <bold> 2.29<gydF4y2Ba/bold></td> <td align="center"> <bold> 0.044<gydF4y2Ba/bold></td> <td align="center">1.33<gydF4y2Ba/td> <td align="center">0.224<gydF4y2Ba/td> <td align="center">1.50<gydF4y2Ba/td> <td align="center">0.157<gydF4y2Ba/td> </tr> <tr> <td align="left">Il1b<gydF4y2Ba/td> <td align="center">1.60<gydF4y2Ba/td> <td align="center">0.125<gydF4y2Ba/td> <td align="center">1.09<gydF4y2Ba/td> <td align="center">0.776<gydF4y2Ba/td> <td align="center">−1.03<gydF4y2Ba/td> <td align="center">0.879<gydF4y2Ba/td> </tr> <tr> <td align="left">Il12a<gydF4y2Ba/td> <td align="center">−1.64<gydF4y2Ba/td> <td align="center">0.113<gydF4y2Ba/td> <td align="center">−1.12<gydF4y2Ba/td> <td align="center">0.532<gydF4y2Ba/td> <td align="center">−1.41<gydF4y2Ba/td> <td align="center">0.226<gydF4y2Ba/td> </tr> <tr> <td align="left">白细胞介素6<gydF4y2Ba/td> <td align="center">1.54<gydF4y2Ba/td> <td align="center">0.363<gydF4y2Ba/td> <td align="center">−2.76<gydF4y2Ba/td> <td align="center">0.219<gydF4y2Ba/td> <td align="center">−1.10<gydF4y2Ba/td> <td align="center">0.656<gydF4y2Ba/td> </tr> <tr> <td align="left">肿瘤坏死因子<gydF4y2Ba/td> <td align="center">1.40<gydF4y2Ba/td> <td align="center">0.138<gydF4y2Ba/td> <td align="center">1.32<gydF4y2Ba/td> <td align="center">0.260<gydF4y2Ba/td> <td align="center">1.24<gydF4y2Ba/td> <td align="center">0.393<gydF4y2Ba/td> </tr> <tr> <td align="left">Ifng<gydF4y2Ba/td> <td align="center">1.06<gydF4y2Ba/td> <td align="center">0.417<gydF4y2Ba/td> <td align="center">2.30<gydF4y2Ba/td> <td align="center">0.124<gydF4y2Ba/td> <td align="center">1.78<gydF4y2Ba/td> <td align="center">0.183<gydF4y2Ba/td> </tr> <tr> <td align="left">Il10<gydF4y2Ba/td> <td align="center">1.49<gydF4y2Ba/td> <td align="center">0.378<gydF4y2Ba/td> <td align="center">−1.36<gydF4y2Ba/td> <td align="center">0.793<gydF4y2Ba/td> <td align="center">1.16<gydF4y2Ba/td> <td align="center">0.776<gydF4y2Ba/td> </tr> <tr> <td align="left">Il1r1<gydF4y2Ba/td> <td align="center">1.39<gydF4y2Ba/td> <td align="center">0.205<gydF4y2Ba/td> <td align="center">1.26<gydF4y2Ba/td> <td align="center">0.446<gydF4y2Ba/td> <td align="center">1.11<gydF4y2Ba/td> <td align="center">0.864<gydF4y2Ba/td> </tr> <tr> <td align="left">Hmgb1<gydF4y2Ba/td> <td align="center">1.09<gydF4y2Ba/td> <td align="center">0.492<gydF4y2Ba/td> <td align="center"> <bold> 1.52<gydF4y2Ba/bold></td> <td align="center"> <bold> 0.042<gydF4y2Ba/bold></td> <td align="center">1.02<gydF4y2Ba/td> <td align="center">0.851<gydF4y2Ba/td> </tr> <tr> <td align="left">Map2k3<gydF4y2Ba/td> <td align="center"> <bold> 1.65<gydF4y2Ba/bold></td> <td align="center"> <bold> 0.021<gydF4y2Ba/bold></td> <td align="center">1.36<gydF4y2Ba/td> <td align="center">0.117<gydF4y2Ba/td> <td align="center">1。2<gydF4y2Ba/td> <td align="center">0.278<gydF4y2Ba/td> </tr> <tr> <td align="left">Il2<gydF4y2Ba/td> <td align="center">−1.27<gydF4y2Ba/td> <td align="center">0.904<gydF4y2Ba/td> <td align="center">4.23<gydF4y2Ba/td> <td align="center">0.258<gydF4y2Ba/td> <td align="center">3.13<gydF4y2Ba/td> <td align="center">0.275<gydF4y2Ba/td> </tr> <tr> <td align="left">Clec4e<gydF4y2Ba/td> <td align="center">1.46<gydF4y2Ba/td> <td align="center">0.372<gydF4y2Ba/td> <td align="center">−2.13<gydF4y2Ba/td> <td align="center">0.184<gydF4y2Ba/td> <td align="center">−1.37<gydF4y2Ba/td> <td align="center">0.724<gydF4y2Ba/td> </tr> <tr> <td align="left">英国网球协会<gydF4y2Ba/td> <td align="center">−1.04<gydF4y2Ba/td> <td align="center">0.572<gydF4y2Ba/td> <td align="center">−2.44<gydF4y2Ba/td> <td align="center">0.351<gydF4y2Ba/td> <td align="center">−1.09<gydF4y2Ba/td> <td align="center">0.952<gydF4y2Ba/td> </tr> <tr> <td align="left">Cd86<gydF4y2Ba/td> <td align="center">−1.11<gydF4y2Ba/td> <td align="center">0.569<gydF4y2Ba/td> <td align="center">−1.12<gydF4y2Ba/td> <td align="center">0.778<gydF4y2Ba/td> <td align="center">−1.52<gydF4y2Ba/td> <td align="center">0.163<gydF4y2Ba/td> </tr> <tr> <td align="left">”丛书<gydF4y2Ba/td> <td align="center">−1.05<gydF4y2Ba/td> <td align="center">0.345<gydF4y2Ba/td> <td align="center">−1.3<gydF4y2Ba/td> <td align="center">0.379<gydF4y2Ba/td> <td align="center">−1.32<gydF4y2Ba/td> <td align="center">0.214<gydF4y2Ba/td> </tr> <tr> <td align="left">Irf1<gydF4y2Ba/td> <td align="center">−1.32<gydF4y2Ba/td> <td align="center">0.451<gydF4y2Ba/td> <td align="center">1.08<gydF4y2Ba/td> <td align="center">0.988<gydF4y2Ba/td> <td align="center">1.02<gydF4y2Ba/td> <td align="center">0.693<gydF4y2Ba/td> </tr> <tr> <td align="left">小君<gydF4y2Ba/td> <td align="center">−1.37<gydF4y2Ba/td> <td align="center">0.340<gydF4y2Ba/td> <td align="center">1.09<gydF4y2Ba/td> <td align="center">0.762<gydF4y2Ba/td> <td align="center">−1.34<gydF4y2Ba/td> <td align="center">0.158<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr1<gydF4y2Ba/td> <td align="center">1.23<gydF4y2Ba/td> <td align="center">0.419<gydF4y2Ba/td> <td align="center">−1.05<gydF4y2Ba/td> <td align="center">0.803<gydF4y2Ba/td> <td align="center">1.06<gydF4y2Ba/td> <td align="center">0.654<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr2<gydF4y2Ba/td> <td align="center"> <bold> 1.73<gydF4y2Ba/bold></td> <td align="center"> <bold> 0.013<gydF4y2Ba/bold></td> <td align="center">1.18<gydF4y2Ba/td> <td align="center">0.320<gydF4y2Ba/td> <td align="center">1.16<gydF4y2Ba/td> <td align="center">0.371<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr3<gydF4y2Ba/td> <td align="center">−1.38<gydF4y2Ba/td> <td align="center">0.320<gydF4y2Ba/td> <td align="center">1.25<gydF4y2Ba/td> <td align="center">0.659<gydF4y2Ba/td> <td align="center">1.11<gydF4y2Ba/td> <td align="center">0.846<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr4<gydF4y2Ba/td> <td align="center">1.49<gydF4y2Ba/td> <td align="center">0.140<gydF4y2Ba/td> <td align="center">1.34<gydF4y2Ba/td> <td align="center">0.251<gydF4y2Ba/td> <td align="center"> <bold> 2.01<gydF4y2Ba/bold></td> <td align="center"> <bold> 0.005<gydF4y2Ba/bold></td> </tr> <tr> <td align="left">Tlr5<gydF4y2Ba/td> <td align="center">−1.09<gydF4y2Ba/td> <td align="center">0.805<gydF4y2Ba/td> <td align="center">1.18<gydF4y2Ba/td> <td align="center">0.815<gydF4y2Ba/td> <td align="center">1.49<gydF4y2Ba/td> <td align="center">0.758<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr6<gydF4y2Ba/td> <td align="center">1.26<gydF4y2Ba/td> <td align="center">0.381<gydF4y2Ba/td> <td align="center">1.02<gydF4y2Ba/td> <td align="center">0.855<gydF4y2Ba/td> <td align="center">1.05<gydF4y2Ba/td> <td align="center">0.960<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr7<gydF4y2Ba/td> <td align="center">−1.37<gydF4y2Ba/td> <td align="center">0.397<gydF4y2Ba/td> <td align="center">−1.44<gydF4y2Ba/td> <td align="center">0.207<gydF4y2Ba/td> <td align="center">−1.29<gydF4y2Ba/td> <td align="center">0.299<gydF4y2Ba/td> </tr> <tr> <td align="left">Tlr9识别<gydF4y2Ba/td> <td align="center">−1.24<gydF4y2Ba/td> <td align="center">0.802<gydF4y2Ba/td> <td align="center">−1.18<gydF4y2Ba/td> <td align="center">0.877<gydF4y2Ba/td> <td align="center">−1.47<gydF4y2Ba/td> <td align="center">0.285<gydF4y2Ba/td> </tr> </tbody> </table> </table-wrap> </sec> </sec> <sec id="sec4"> <title>4所示。讨论<gydF4y2Ba/title> <p>大量实验研究发现抗炎作用的n - 3 PUFA在肠道炎症随机临床试验没能证明疗效[<gydF4y2Baxref ref-type="bibr" rid="B2"> 2<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B23"> 23<gydF4y2Ba/xref>]。我们之前假设之间的差异的临床试验和实验研究结果从干预的时机<gydF4y2Baxref ref-type="bibr" rid="B23"> 23<gydF4y2Ba/xref>]。在我们先前的研究在结肠炎模型(<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B19"> 19<gydF4y2Ba/xref>),我们测试了与n - 3 PUFA营养干预治疗的方式。我们现在推测营养干预与脂肪酸应该预防反映在流行病学研究。在流行病学研究中,膳食摄入PUFA修改IBD的风险,现在需要和识别潜在的机制。为了这个目的,我们喂大鼠4周的饮食不同的PUFA结肠炎的发病前组成。<gydF4y2Ba/p> <p>在目前的研究中,n - 3饮食下调结肠伊诺表达式(图<gydF4y2Baxref rid="fig2a" ref-type="fig"> 2(一个)<gydF4y2Ba/xref>)在大鼠TNBS-induced结肠炎类似于先前的研究由我们(<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B19"> 19<gydF4y2Ba/xref>)或其他(<gydF4y2Baxref ref-type="bibr" rid="B21"> 21<gydF4y2Ba/xref>]。的确,n - 3 PUFA可以调节氧化应激。Camuesco等<gydF4y2Baitalic> 。<gydF4y2Ba/italic>发现,橄榄油富含鱼油氧化活性降低了还原谷胱甘肽浓度和减少大鼠的结肠伊诺表达式<gydF4y2Baxref ref-type="bibr" rid="B21"> 21<gydF4y2Ba/xref>]。饮食n PUFA发挥抗炎作用。事实上,n - 3饮食减少结肠cox - 2和结肠LTB4生产(图<gydF4y2Baxref rid="fig3" ref-type="fig"> 3<gydF4y2Ba/xref>)。这结果是按照我们先前的研究显示营养干预的抑制作用与n - 3 PUFA cox - 2和LTB4<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B19"> 19<gydF4y2Ba/xref>]。同样,它已经表明,得罪花生四烯酸acid-derived类花生酸减少炎症和小鼠结肠炎严重程度(<gydF4y2Baxref ref-type="bibr" rid="B28"> 28<gydF4y2Ba/xref>]。此外,变更类花生酸是PUFA的主要机制之一<gydF4y2Baxref ref-type="bibr" rid="B29"> 29日<gydF4y2Ba/xref>]。在目前的研究中,n - 3饮食也下调结肠促炎细胞因子il - 6等(图<gydF4y2Baxref rid="fig2c" ref-type="fig"> 2 (c)<gydF4y2Ba/xref>)和倾向于降低TNF<gydF4y2Baitalic> α<gydF4y2Ba/italic>生产。<gydF4y2Ba/p> <p>在目前的研究中,IL-1A基因表达调节了n - 3饮食(表<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。这个结果是符合的<gydF4y2Baitalic> 在体外<gydF4y2Ba/italic>研究表明,EPA治疗增加IL-1A人类角质细胞(分泌<gydF4y2Baxref ref-type="bibr" rid="B30"> 30.<gydF4y2Ba/xref>]。在我们的研究中,我们观察到显著降低il - 6生产(图<gydF4y2Baxref rid="fig2c" ref-type="fig"> 2 (c)<gydF4y2Ba/xref>(表),而il - 6基因表达没有区别<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。差异基因表达和蛋白质浓度经常发现在文献中。在先前的研究中,我们观察到TNBS管理导致肿瘤坏死因子增加了60%<gydF4y2Baitalic> α<gydF4y2Ba/italic>生产,观察基因表达的的12倍<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>]。研究测试基因表达和蛋白质含量之间的相关性发现,信使rna和蛋白质丰度差异表达,表明频繁的转录后的调控基因表达的<gydF4y2Baxref ref-type="bibr" rid="B31"> 31日<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>饮食n PUFA TLR2基因相比,控制饮食而增加n - 9饮食增加TLR4基因(表<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。在文献中,n - 3 PUFA的抑制作用TLR2是有争议的。TLR2蛋白表达下调了EPA在老鼠的脂肪干细胞(<gydF4y2Baxref ref-type="bibr" rid="B32"> 32<gydF4y2Ba/xref>]在研究调查的影响范围的饱和脂肪和不饱和脂肪TLR2和TLR4激活没有发现影响(<gydF4y2Baxref ref-type="bibr" rid="B33"> 33<gydF4y2Ba/xref>]。本研究的调查人员并没有发现任何影响DHA, EPA、油酸激活TLR2和TLR4 HEK-Blue细胞(<gydF4y2Baxref ref-type="bibr" rid="B33"> 33<gydF4y2Ba/xref>]。然而,这些脂肪酸能够表达下调肿瘤坏死因子等细胞因子的生产<gydF4y2Baitalic> α<gydF4y2Ba/italic>、il - 6和MCP-1分泌在人类脂肪组织和脂肪细胞的培养<gydF4y2Baxref ref-type="bibr" rid="B33"> 33<gydF4y2Ba/xref>]。我们研究饮食对TLR表达的影响但我们没有探索其对肠道菌群的影响。它已经表明,鱼油能够减弱n-6 PUFA-induced失调在结肠炎模型(<gydF4y2Baxref ref-type="bibr" rid="B34"> 34<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>饮食n-6增加高机动组的基因表达盒1 (HMGB1,表<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。增加结肠癌HMGB1的膳食n-6 PUFA观察在大鼠结肠癌(<gydF4y2Baxref ref-type="bibr" rid="B35"> 35<gydF4y2Ba/xref>]。HMGB1可以激活多种信号通路如TLR但我们没有观察到任何增加TLR信号通过n-6饮食。其他信号通路受体等先进的糖化终端产品(愤怒)信号可能涉及<gydF4y2Baxref ref-type="bibr" rid="B36"> 36<gydF4y2Ba/xref>]。事实上,增加愤怒通过膳食n-6据报道在实验性结肠癌模型(<gydF4y2Baxref ref-type="bibr" rid="B37"> 37<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>除了il-1a MAP2k3, TLR基因,我们观察到只有温和的n - 3饮食在炎症基因表达的影响。与其他的研究中,我们旨在评估膳食影响n - 3 PUFA创世纪炎症而大量研究感兴趣的药理效应的n - 3 PUFA治疗的方式(<gydF4y2Baxref ref-type="bibr" rid="B21"> 21<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B38"> 38<gydF4y2Ba/xref>]。许多研究已经使用长链n PUFA [<gydF4y2Baxref ref-type="bibr" rid="B39"> 39<gydF4y2Ba/xref>)在本研究中使用的实验饮食不包含任何长链PUFA;这些饮食不能直接复制一个典型的人类饮食杂食者。给药途径也是一个关键,我们使用饮食不同不饱和脂肪酸组成,n - 3 PUFA通常由填喂法。这些实验设计差异可以解释我们对炎症基因表达的影响。<gydF4y2Ba/p> <p>脂肪酸是HNF-4内源性配体<gydF4y2Baitalic> α<gydF4y2Ba/italic>(<gydF4y2Baxref ref-type="bibr" rid="B40"> 40<gydF4y2Ba/xref>],HNF-4的角色<gydF4y2Baitalic> α<gydF4y2Ba/italic>在肠道炎症体内平衡已被证实在小鼠肠道上皮HNF-4删除<gydF4y2Baitalic> α<gydF4y2Ba/italic>(<gydF4y2Baxref ref-type="bibr" rid="B41"> 41<gydF4y2Ba/xref>]。我们假设饮食PUFA可以调节HNF-4但我们没有观察结肠HNF-4的任何修改<gydF4y2Baitalic> α<gydF4y2Ba/italic>组间表达。同样,核受体PPAR<gydF4y2Baitalic> γ<gydF4y2Ba/italic>可以激活PUFA和调节器的肠道炎症<gydF4y2Baxref ref-type="bibr" rid="B42"> 42<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B43"> 43<gydF4y2Ba/xref>),但其表达不是不同的组间。<gydF4y2Ba/p> <p>饮食PUFA并不影响屏障功能在我们的研究中。我们调查紧密连接蛋白MUC2和TFF3 mRNA水平,我们并没有发现任何显著的影响在组织(图<gydF4y2Baxref rid="fig4" ref-type="fig"> 4<gydF4y2Ba/xref>)。一些研究发现n - 3 PUFA屏障功能的保护作用。Hudert等人使用转基因老鼠携带<gydF4y2Baitalic> 秀丽隐杆线虫脂肪1<gydF4y2Ba/italic>基因编码一种n - 3脂肪酸desaturase n-6转化为n - 3脂肪酸,他们诱导DSS结肠炎在这些老鼠<gydF4y2Baxref ref-type="bibr" rid="B44"> 44<gydF4y2Ba/xref>]。他们发现,<gydF4y2Baitalic> 脂肪1<gydF4y2Ba/italic>老鼠免受结肠炎感应与野生型小鼠相比与降低炎症标记物(<gydF4y2Baxref ref-type="bibr" rid="B44"> 44<gydF4y2Ba/xref>]。他们还发现,脂肪1小鼠表现出增加的生产防护标志,如TFF3 [<gydF4y2Baxref ref-type="bibr" rid="B44"> 44<gydF4y2Ba/xref>]。鱼油补充剂与TNBS-induced结肠炎大鼠的数量也增加了与成熟的杯状细胞粘蛋白颗粒(<gydF4y2Baxref ref-type="bibr" rid="B38"> 38<gydF4y2Ba/xref>]。然而,我们的实验设计是不同于这些研究。事实上,我们调查的影响在饮食PUFA剂量虽然以前的研究调查PUFA immunonutrients。<gydF4y2Ba/p> <p>在目前的研究中,n - 3饮食组显示n / n-6比率等于1减毒在结肠炎症标记物。这种预防性的方法已经在小型临床试验进行测试。在日本的一项研究中,n - 3在IBD患者饮食治疗的功效已经评估(<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>]。这项研究的作者双重营养相结合的方法实现n / n-6比1患者的饮食建议和营养补充(<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>]。病人被禁止食用的主要来源n-6 PUFA消费如植物油或敷料。他们还提供了一个n - 3 PUFA补充食物交换表特权和n - 3 (<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>]。这项研究的作者发现,n - 3 / n-6比缓解组(<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>]。在挪威的一项研究中,他们评估的影响600 g的鲑鱼消费8周的每周12活跃UC患者和他们发现减少临床炎症指数(<gydF4y2Baxref ref-type="bibr" rid="B45"> 45<gydF4y2Ba/xref>]。概念验证研究现在需要评估n PUFA预防的方式。我们不能直接针对炎症性肠病生理病理学与营养治疗炎症性肠病诊断之前,我们可能首先评估n - 3 CD术后患者的治疗。事实上,术后阶段被认为是一个完美的窗口评估诱发炎症性肠病的复发因素。<gydF4y2Ba/p> <p>同样的,在最近的流行病学研究,女人与审慎的饮食(特点是摄入更多的水果、蔬菜和鱼)风险降低CD [<gydF4y2Baxref ref-type="bibr" rid="B15"> 15<gydF4y2Ba/xref>]。此外,更大的摄入鱼(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M43"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>趋势= 0.01)已明确的风险降低CD [<gydF4y2Baxref ref-type="bibr" rid="B15"> 15<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>总之,谨慎的n - 3 / n-6比率高的饮食可能导致部分限制结肠炎创世纪。进一步的研究将是强制性的,以确定机制饮食效果更好的饮食建议定义一个科学原理。<gydF4y2Ba/p> </sec> <back> <sec> <title>的利益冲突<gydF4y2Ba/title> <p>作者宣称没有利益冲突。<gydF4y2Ba/p> </sec> <ref-list> <ref id="B1" content-type="article"> <label>1<gydF4y2Ba/label> <element-citation publication-type="journal"> <person-group person-group-type="author"> <name> <surname> Baumgart<gydF4y2Ba/surname> <given-names> d . 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