氯沙坦降低三硝基苯磺酸诱导的大鼠结肠纤维化

摘要

肠纤维化是一种由多种因素介导的慢性进行性过程，常发生在纤维狭窄性肠病中，但最常发生在克罗恩病(CD)患者中。尽管在过去的20年里，对乳糜泻及其治疗的认识取得了进步，但手术干预仍然是纤维狭窄型乳糜泻患者的唯一治疗策略。然而，一些研究的结果表明，纤维化可能是可逆和/或可预防的现象。在概述了细胞、细胞因子和生长因子相互作用导致炎症和纤维化进展的当代知识之后，这篇文章描述了类似于人CD的结肠炎实验动物模型，作者用来研究氯沙坦，背景:在几种纤维狭窄性肠病中，肠道纤维化是一种具有挑战性的临床条件，特别是克罗恩病。目前对肠纤维化尚无有效的预防措施和药物治疗。纤维化是细胞/基质/细胞因子和生长因子相互作用介导的慢性进行性过程，但可能是可逆的现象。在调节纤维形成的几个分子中，转化生长因子-β1 (TGF-β1)似乎起着关键作用;它是由血管紧张素II的局部激活强烈诱导的。TGF-β1和血管紧张素II在纤维狭窄性克罗恩病中均升高。目的:评价血管紧张素II受体拮抗剂氯沙坦对慢性结肠炎相关纤维化过程和TGF-β1表达的体内作用。METHODS: Colitis was induced by intrarectal instillation of trinitrobenzene sulphonic acid (TNBS) (15 mg/mL) while losartan was administered orally daily by gavage (7 mg/kg/day) for 21 days. Three groups of rats were evaluated: control (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and fibrosis of the colon were evaluated by macro- and microscopic score analysis. Colonic TGF-β1 levels was measured using ELISA.RESULTS: Twenty-one days after induction, losartan significantly improved the macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-β1 concentration.CONCLUSIONS: Prophylactic oral administration of losartan reduces the colorectal fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to be mediated by a downregulation of TGF-β1 expression.

加拿大胃肠病学和肝病杂志

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