白藜芦醇在蛛网膜下腔出血后缓解氧化应激性损伤

Resveratrol Ameliorate Oxidative Stress after Experimental Subarachnoid Hemorrhage

本研究将探寻白藜芦醇(resveratrol,RSV)在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后的抗氧化作用及相关机制.实验一,60只大鼠随机分配到sham组和SAH各时间点组,检测SIRT1、PGC-1α在各组中蛋白水平的变化.实验二,100只大鼠随机分配到sham组、SAH组、SAH+vehicle组、SAH+RSV组和SAH+RSV+EX527组,给予RSV或同时给予RSV和抑制剂EX527,检测SIRT1和PGC-1α的变化以及对应的氧化应激指标、脑水肿和神经功能评分的变化.结果显示,实验一,SIRT1和PGC-1α在SAH后升高并在24 h达到高峰,较sham组明显升高(p<0.05).实验二,经RSV治疗,SAH后SIRT1和PGC-1α明显升高,且对应的氧化应激性损伤和脑水肿较SAH+vehicle组明显缓解、神经功能评分明显降低(p<0.05);经EX527处理后,RSV在SAH后的保护作用明显下调(p<0.05).结论 RSV在SAH后具有抗氧化作用,且这种抗氧化效果主要通过激活SIRT1/PGC-1α通路实现.

It has been reported that resveratrol(RSV)can ameliorate injury after subarachnoid hemorrhage(SAH).The aim here is to elucidate the antioxidant function of RSV after SAH.In experimental 1,brain SIRT1 and PGC-1αprotein levels were examined in different groups after SAH induction.In experimental 2,rats were divided into 5 groups:sham group,SAH group,SAH+vehicle group,SAH+RSV group,and SAH+RSV+EX527 group.The SIRT1 activator RSV and specific inhibitor EX527 were respectively administered.Then,Western blot,Immunofluorescence staining,oxidant/antioxidant factors,brain edema,and neurologic scoring were performed.After experimental SAH was induced,the nuclear SIRT1 and PGC-1αprotein level increased from 6 h to 12 h,with a peak at 24 h,but gradually decreased from 48 h.RSV treatment in SAH rats led to a significant increment of SIRT1 and PGC-1αprotein levels resulting in an enhancement of antioxidant effect when compared with SAH rats without treatment.The antioxidant effect of RSV in SAH rats could be partially abrogated by the SIRT1 inhibitor EX527.These results show that RSV has an antioxidant effect after SAH via the SIRT1/PGC-1αsignaling pathway.