还原型谷胱甘肽保护线粒体并减轻大鼠肝脏缺血再灌注损伤

【】 目的 探讨还原型谷胱甘肽(GSH)减轻肝脏缺血再灌注(IR)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。除假手术组外,其余组建立70%大鼠肝IR损伤模型,肝脏缺血时间为60 min。GSH组于缺血前5 min经大鼠股静脉注射5mg/kg的GSH。再灌注24h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。比较各组组织GSH/GSSG率,检测各组肝细胞线粒体钙容纳力(CRC)。结果 与I/R组比较,再灌注后GSH组血清AST和ALT均明显降低(P＜0.05)。再灌注24 h,与I/R组比较, GSH组肝组织损伤明显减轻,凋亡细胞数显著减少(P＜0.05)；同时,肝组织GSH/GSSG比值明显增加(P＜0.05)；再灌注后24 h,与I/R组比较,GSH组肝细胞线粒体钙容纳力明显增加。结论 GSH预处理能减轻大鼠肝脏I/R损伤,该作用可能与减少氧化应激,从而抑制mPTP开放有关。

Glutathione protects mitochondrion and alleviates liver ischemia-reperfusion injury in rats

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 h after 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 6 h after reperfusion compared with I/R group(P<0.05). 24 h after 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 6 h after reperfusion compared with I/R group (P<0.05). Liver mitochondrial CRC in GSH group was significantly increased 6 h after 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.