Department of Gastroenterology, Guangzhou Huadu District People's Hospital, Guangzhou, China.
Contrast Media Mol Imaging. 2022 Jul 15;2022:3301330. doi: 10.1155/2022/3301330. eCollection 2022.
This study aims to investigate the mechanism by which biliary drainage reduces intestinal barrier damage in obstructive jaundice (OJ). A biliary drainage model was established in rats with OJ to detect changes in inflammatory factors and diamine oxidase (DAO), a marker of intestinal mucosal damage. The expression of autophagy-related genes in the intestinal mucosa after biliary drainage was detected using a reverse transcription-polymerase chain reaction. The rats were separated into two groups that received the autophagy activator rapamycin (RAPA) or the autophagy inhibitor 3-methyladenine (3-MA) to further investigate whether biliary drainage could alleviate the inflammatory response, oxidative stress, mitochondrial complex IV damage, and thus barrier damage in rats with OJ. The expression levels of inflammatory factors and the serum DAO content were increased in rats with OJ ( < 0.05). Biliary drainage further induced autophagy, reduced the expression levels of inflammatory factors, decreased the serum DAO content ( < 0.05), and improved intestinal mucosal damage. Administration of RAPA to OJ rats with biliary drainage increased autophagy ( < 0.05); decreased inflammatory factor secretion ( < 0.05), the serum DAO content ( < 0.05), oxidative stress ( < 0.05), and mitochondrial respiratory chain complex IV damage ( < 0.05); and ameliorated intestinal mucosal injury in OJ rats. When OJ rats were treated with 3-MA, intestinal mucosal injury, intestinal mitochondrial injury, and oxidative stress were all aggravated ( < 0.05). Biliary drainage can reduce the expression of inflammatory factors, oxidative stress, and mitochondrial injury by inducing intestinal mucosal autophagy in OJ rats, thus suggesting its role in the alleviation of intestinal mucosal injury.
本研究旨在探讨胆道引流减轻梗阻性黄疸（OJ）肠道屏障损伤的机制。建立 OJ 大鼠胆道引流模型，检测炎症因子和二胺氧化酶（DAO）变化，DAO 是肠黏膜损伤的标志物。采用逆转录-聚合酶链反应检测胆道引流后肠黏膜自噬相关基因的表达。将大鼠分为接受自噬激活剂雷帕霉素（RAPA）或自噬抑制剂 3-甲基腺嘌呤（3-MA）的两组，进一步探讨胆道引流是否能减轻 OJ 大鼠的炎症反应、氧化应激、线粒体复合物 IV 损伤，从而减轻肠道屏障损伤。OJ 大鼠炎症因子和血清 DAO 含量升高（<0.05）。胆道引流进一步诱导自噬，降低炎症因子表达水平，降低血清 DAO 含量（<0.05），改善肠黏膜损伤。胆道引流 OJ 大鼠给予 RAPA 增加自噬（<0.05）；减少炎症因子分泌（<0.05）、血清 DAO 含量（<0.05）、氧化应激（<0.05）和线粒体呼吸链复合物 IV 损伤（<0.05）；改善 OJ 大鼠肠黏膜损伤。OJ 大鼠给予 3-MA 时，肠黏膜损伤、肠线粒体损伤和氧化应激均加重（<0.05）。胆道引流通过诱导 OJ 大鼠肠黏膜自噬减少炎症因子、氧化应激和线粒体损伤，从而减轻肠黏膜损伤。
