Joh T, Ikai M, Oshima T, Kurokawa T, Seno K, Yokoyama Y, Okada N, Itoh M
First Department of Internal Medicine, Nagoya City University School of Medicine, Nagoya, Japan.
Life Sci. 2001 Nov 21;70(1):109-17. doi: 10.1016/s0024-3205(01)01385-6.
Ischemia-reperfusion (I/R) of stomach causes gastric mucosal injury. Complement can also cause tissue damage, however its role in gastric I/R injury has not been thoroughly investigated. We evaluated the effect of complement suppression in reducing damage to the gastric epithelium caused by local I/R. Local gastric ischemia was induced by clamping the left gastric artery. The blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. 51Cr-EDTA clearance increased shortly after reperfusion with peak values at 10 min. Intraperitoneal administration of cobra venom factor (CVF; 50 units) prior to I/R, which reduced the serum complement value (CH50) to an undetectable level, remarkably suppressed the 51Cr-EDTA clearance following reperfusion. A monocarboxylic acid derivative of K-76 (K-76 COOH) reduced the CH50 by more than 30% (100 mg/kg) and 60% (200 mg/kg). Rats pretreated with K-76 significantly attenuated the increase in 51Cr-EDTA clearance produced by I/R. These results suggest that complement inhibitor could be used to protect gastric mucosal injury induced by local I/R stress.
胃缺血再灌注（I/R）会导致胃黏膜损伤。补体也可引起组织损伤，然而其在胃I/R损伤中的作用尚未得到充分研究。我们评估了补体抑制在减轻局部I/R所致胃上皮损伤方面的作用。通过夹闭胃左动脉诱导局部胃缺血。以51Cr标记的依地酸（51Cr-EDTA）的血-腔清除率作为上皮损伤的指标。再灌注后不久51Cr-EDTA清除率即升高，在10分钟时达到峰值。在I/R前腹腔注射眼镜蛇毒因子（CVF；50单位），可将血清补体值（CH50）降至检测不到的水平，显著抑制再灌注后51Cr-EDTA的清除率。K-76的单羧酸衍生物（K-76 COOH）（100 mg/kg）使CH50降低超过30%，（200 mg/kg）降低超过60%。预先用K-76处理的大鼠显著减轻了I/R所致51Cr-EDTA清除率的升高。这些结果表明，补体抑制剂可用于保护局部I/R应激诱导的胃黏膜损伤。
