摘要
目的探讨还原型谷胱甘肽(GSH)减轻肝脏缺血再灌注(I/R)损伤的作用及机制。方法将成年SD大鼠分为假手术组、I/R组和GSH组,每组20只。除假手术组外,其余组建立70%大鼠肝I/R损伤模型,肝脏缺血时间为60min。GSH组大鼠于缺血前5min经股静脉注射5mg/kg的GSH。再灌注后通过血清学和组织学指标观察肝损伤情况,TUNEL染色评价肝细胞凋亡。比较各组肝组织GSH与氧化型谷胱甘肽(GSSG)的比值(GSH/GSSG比值),检测各组肝细胞线粒体钙容纳力(CRC)。结果与I/R组比较,再灌注6h后GSH组血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)均降低(P<0.05)。再灌注24h,与I/R组比较,GSH组肝组织损伤减轻,凋亡细胞数目减少(P<0.05);同时,再灌注6h后GSH组肝组织GSH/GSSG比值较I/R组增加(P<0.05);与I/R组比较,再灌注后6hGSH组肝细胞线粒体CRC增加(P<0.05)。结论 GSH预处理能减轻大鼠肝脏I/R损伤,该作用可能与减轻线粒体氧化应激,从而抑制线粒体通透性转换孔开放有关。
Objective To investigate the protective effects of glutathione（GSH）against hepatic ischemia/reperfusion（I/R）injury and the related mechanism.Methods SD rats were randomized into Sham,I/R and GSH groups with 20 rats in each group.Rat models of segmental（70%）warm hepatic ischemia were established in I/R and GSH groups.GSH was injected through the femoral vein at the dose of 5 mg/kg 5 min before ischemia.At 24 hafter reperfusion,liver injury was evaluated by serological and histological indices.Liver cell apoptoses were evaluated by TUNEL staining.The GSH/oxidized glutathione（GSSG）ratios of tissue level were compared between different groups.Liver mitochondria were collected and the mitochondrial calcium capacity（CRC）was evaluated.Results The serum aspartate transaminanse（AST）and alanine aminotransferase（ALT）levels in GSH group were significantly decreased 6hafter reperfusion compared with I/R group（P〈0.05）.24 hafter reperfusion,the liver injury was alleviated and the number of apoptosis cells was significantly decreased in GSH group compared with I/R group（P〈0.05）.The GSH/GSSG ratio of tissue level in GSH group was significantly increased 6hafter reperfusion compared with I/R group（P〈0.05）.Liver mitochondrial CRC in GSH group was significantly increased 6hafter reperfusion compared with I/R group（P〈0.05）.Conclusion GSH preconditioning can protect liver from hepatic I/R injury,which is possibly by inhibiting oxidative response and subsequent inhibition of mitochondrial permeability transition.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2015年第12期1300-1303,共4页
Academic Journal of Second Military Medical University
基金
国家自然科学基金青年基金(81300344)
上海市卫计委重点项目(20120708)
上海市科委生物医药引导项目(124119a3601)~~
关键词
肝
再灌注损伤
谷胱甘肽
线粒体
liver
reperfusion injuries
glutathione
mitochondria
