Pathogenic importance of pepsin in ischemia/reperfusion-induced gastric injury
Pathogenic importance of pepsin in ischemia/reperfusion-induced gastric injury
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DOI：
10.1016/j.lfs.2007.02.041
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发表时间：
2007-05-01
期刊：
影响因子：
6.1
通讯作者：
Takeuchi, Koji
中科院分区：
文献类型：
--
作者：
Kotani, Tohru;Murashima, Yukiko;Takeuchi, Koji
我们研究了胃蛋白酶在大鼠缺血/再灌流(I/R)诱导的胃损伤中的作用。乌拉坦麻醉下，结扎幽门，夹闭腹腔动脉，胃内注入盐酸1ml(50~150 mm)。15min后取钳夹建立再灌流模型，2 h后观察胃黏膜大体损伤情况。给予胃抑素(一种特定的胃酶抑制剂)或胃酶。结扎幽门，同时皮下注射西咪替丁、奥美拉唑或阿托品。结扎前30分钟。大鼠I/R可引起出血性胃损伤，并伴有胃蛋白酶分泌量的增加，其程度与盐酸浓度有关。阿托品或双侧迷走神经切断术均可显著预防100 mM盐酸诱导的IR损伤，但奥美拉唑和西咪替丁均无此作用。胃抑素灌胃可剂量依赖性地减轻I/R引起的胃损伤，即使在0.1 mg/kg时作用也非常显著，而胃蛋白酶则明显加重这些损伤。I/R期间胃酶产量的增加与胃酸丢失有关，双侧迷走神经切断或阿托品预处理可显著抑制胃酶活性，而西咪替丁或奥美拉唑无明显作用，胃抑素则显著抑制胃酶活性。综上所述，我们认为胃蛋白酶在胃I/R损伤的发病机制中起关键作用，在I/R过程中胃蛋白酶的分泌增加，这一过程与酸的反扩散有关，并通过迷走神经-胆碱能途径介导。(C)2007 Elsevier Inc.保留所有权利：
We investigated the role of pepsin in the development of ischemia/reperfusion (I/R)-induced gastric lesions in rats. Under urethane anesthesia, the pylorus was ligated, the celiac artery was clamped, and 1 ml of HCl (50-150 mM) was instilled in the stomach. Then, reperfusion was established 15 min later by removing the clamp, and 2 h later the stomach was assessed for gross mucosal damage. Pepstatin (a specific pepsin inhibitor) or pepsin was given i.g. after the pylorus was ligated while cimetidine, omeprazole, or atropine was given s.c. 30 min before the ligation. I/R produced hemorrhagic gastric injury, with a concomitant increase in the amount of pepsin secreted, and the degree of both these responses was dependent on the concentration of HCL The formation of lesions by IR in the presence of 100 mM HCl was significantly prevented by atropine or bilateral vagotomy, but neither omeprazole nor cimetidine had any effect. Intragastric administration of pepstatin dose-dependently reduced the severity of the I/R-induced gastric lesions, the effect being significant even at 0.1 mg/kg, while that of pepsin markedly aggravated these lesions. The increased pepsin output during I/R was associated with luminal acid loss and significantly inhibited by bilateral vagotomy or pretreatment with atropine but not cimetidine or omeprazole, while pepstatin significantly inhibited the pepsin activity. In conclusion, we suggest that pepsin plays a pivotal role in the pathogenesis of I/R-induced gastric lesions, and pepsin secretion is increased during I/R the process being associated with acid back-diffusion and mediated through a vagal-cholinergic pathway. (C) 2007 Elsevier Inc. All rights reserved: