人参皂苷Rg1对大鼠脑缺血再灌注损伤细胞凋亡的影响

Effects of ginsenoside Rg1 on apoptosis induced by transient focal cerebral ischemia in rats

目的:研究人参皂苷Rg1对大鼠脑缺血再灌注损伤时细胞凋亡的影响。方法:采用大鼠右侧大脑中动脉阻断(middle cerebral artery occulusion,MCAO)局灶性脑缺血再灌注模型,缺血前给予人参皂苷Rg1 25、501、00 mg.kg-1灌胃,7 d。末次给药1h后制备MCAO模型,缺血2 h,再灌注22 h后,分别用Longa’s法T、TC染色法评价大鼠的神经功能状态及脑梗死面积;用TUNEL法测定缺血再灌后神经细胞凋亡的程度;用Western blot法测定大脑缺血侧脑组织中与凋亡相关基因Caspase-3、Bcl-2的蛋白表达。结果:人参皂苷Rg1(50、100 mg.kg-1)可明显减少MCAO再灌注后脑梗死面积,改善神经功能症状,与模型组比较具有显着性差异(P<0.05或P<0.01);脑缺血2 h再灌22 h后,模型组大鼠缺血侧细胞凋亡程度、Caspase-3蛋白表达明显增加,同时Bcl-2的蛋白表达降低。给予人参皂苷Rg1(50,100mg.kg-1)后,缺血侧细胞凋亡程度、Caspase-3蛋白表达降低,而Bcl-2的蛋白表达增加,与模型组相比具有统计学意义(P<0.01或P<0.05)。结论:人参皂苷Rg1对大鼠脑缺血再灌注损伤引起的细胞凋亡具有明显的保护作用,其机理可能与人参皂苷Rg1影响Caspase-3、Bcl-2的表达有关。

AIM： To investigate the inhibiting effects and mechanism of ginsenoside Rgl on apoptosis following focal cerebral ischemia/reperfusion （I/R）. METHODS;： Rats were pretreated with ginsenoside Rgl at the dose of 25,50 and 100 mg·kg^-1 ig for 7 d, respectively, and then subjected to cerebral ischemia/ reperfusion （I/R） injury induced by a middle cerebral artery occlusion （MCAO）. After 2 h ischemia and 22 h reperfusion, the infarct volume and the neurological deficit were determined by 2, 3, 5-triphenyltetrazolium chloride （ TIC ） staining and Longa＇s score, in situ end-labeling of nuclear DNA fragmentation （TUNEL） were employed to determine the level of apoptosis. The protein expressions of Caspase-3 and Bcl-2 in brain tissue were determined by Western blot.RESULTS： Ginsenoside Rgl significantlyreduced infarct volume and ameliorated the neurological deficit （P 〈 0.05 or P 〈 0.01）. The increase of TUNEL-positive staining cells and Caspase-3 expression, and the decrease of Bcl-2 expression were significantly observed in vehicle-operated group after 22 h repeffusion. Ginsenoside Rgl （50 and 100 mg·kg^-1） markedly inhibited apoptosis and the expression of Caspase-3, and upregulated the expression of Bel-2 after cerebral I/R （ P 〈 0.05, P 〈 0.01 vs vehicle-treated）. CONCLUSION： Ginsenoside Rgl has protective effects on cerebral injury through affecting the expressions of Caspase-3 and Bcl-2 after I/R injury.