TY -的A2 Tahmasbpour Eisa盟——刘昱盟——刘,瑞盟——黄,Lei AU -左,帮派AU -戴,嘉兴AU -高,凌AU -史,回族盟方,任命非盟- Lu,秦盟——冈田克也、武盟——王,Zhifei盟,胡小盟——Lenahan卡梅隆AU - Tang Jiping盟——小杰盟——张,John h . PY - 2022 DA - 2022/12/09 TI -抑制前列腺素E2受体EP3变弱氧化应激和神经细胞凋亡部分调制p38MAPK进行Mfn2 / FOXO3 / Mul1 /通路在大鼠蛛网膜下腔出血后SP - 7727616六世- 2022 AB -氧化应激和神经细胞凋亡导致早期脑损伤的病理过程(EBI)蛛网膜下腔出血(SAH)后。先前的研究表明,抑制前列腺素E2受体EP3抑制氧化应激和凋亡的影响仅次于阿尔茨海默病和脑内出血。本研究旨在调查EP3的抗氧化应激和凋亡效应抑制和大鼠SAH模式的潜在机制。总共有263 Sprague-Dawley雄性老鼠。SAH引起血管内穿孔。选择性EP3拮抗剂L798106鼻内接种1 h, h, 25到49岁h SAH后归纳。EP3淘汰赛CRISPR FOXO3激活CRISPR intracerebroventricularly管理在48小时前长官,而选择性EP3兴奋剂sulprostone SAH之前在1 h。SAH年级、神经赤字,西方的屁股,免疫荧光染色,Fluoro-Jade C染色,TUNEL染色,8-OHdG染色和尼氏小染色SAH后进行。内源性PGES2的表达增加,达到12 h在EP1的表达,EP2 EP3 EP4, Mul1增加,达到峰值后24 h在大脑侧长官。EP3主要表达在神经元。 The inhibition of EP3 with L798106 or EP3 KO CRISPR ameliorated the neurological impairments, brain tissue oxidative stress, and neuronal apoptosis after SAH. To examine potential downstream mediators of EP3, we examined the effect of the increased expression of activated FOXO3 following the administration of FOXO3 activation CRISPR. Mechanism studies demonstrated that L798106 treatment significantly decreased the expression of EP3, p-p38, p-FOXO3, Mul1, 4-HNE, Bax, and cleaved caspase-3 but upregulated the expression of Mfn2 and Bcl-2 in SAH rats. EP3 agonist sulprostone or FOXO3 activation CRISPR abolished the neuroprotective effects of L798106 and its regulation on expression of p38MAPK/FOXO3/Mul1/Mfn2 in the ipsilateral brain after SAH. In conclusion, the inhibition of EP3 by L798106 attenuated oxidative stress and neuronal apoptosis partly through p38MAPK/FOXO3/Mul1/Mfn2 pathway post-SAH in rats. EP3 may serve as a potential therapeutic target for SAH patients. SN - 1942-0900 UR - https://doi.org/10.1155/2022/7727616 DO - 10.1155/2022/7727616 JF - Oxidative Medicine and Cellular Longevity PB - Hindawi KW - ER -