黄芪甲苷对局灶性脑缺血再灌注后神经细胞凋亡的影响

Influence of Astragaloside IV on Nerve Cells Apoptosis after Focal Cerebral Ischemia/Reperfusion

目的:探讨黄芪甲苷对大鼠局灶性脑缺血再灌注后神经细胞凋亡及凋亡相关基因蛋白[bcl-2、Bax、caspase-3、核转录因子кB(NF-кB)]的影响。方法:采用改良的线栓法建立大鼠局灶性脑缺血再灌注模型48只;设假手术组,模型组,黄芪甲苷低、中、高剂量组和银杏叶提取物组(阳性药对照组),每组8只。再灌注24小时后,行神经功能评分,测定脑组织含水量和脑梗死体积;观察神经细胞凋亡状况,测定脑组织中凋亡相关基因和蛋白表达。结果:与模型组比较,黄芪甲苷中、高剂量组大鼠神经功能评分显著降低、神经功能明显改善,脑组织含水量和梗死体积显著降低(P<0.05);黄芪甲苷低、中、高剂量组大鼠神经细胞凋亡状况明显好转,其中黄芪甲苷高剂量组最为显著,黄芪甲苷中、高剂量组凋亡指数(AI)显著降低(P<0.05);凋亡相关基因Bax m RNA表达显著下调且bcl-2 m RNA显著上调、bcl-2/Bax值显著升高(P<0.05),caspase-3、NF-кB蛋白表达均显著下调(P<0.05)。结论:黄芪甲苷对局灶性脑缺血再灌注大鼠神经细胞凋亡具有抑制作用,可能与调节凋亡相关基因和蛋白表达有关。

Objective:To discuss the effects of astragaloside Ⅳ on nerve cells apoptosis after focal cerebral ischemia/reperfusion and the apoptosis-related gene protein including bcl-2,Bax,caspase-3,and nuclear factor-кB(NF-кB).Methods:Modified suture method was used to establish the rat models with focal cerebral ischemia/reperfusion,divided into sham operation group,the model group,low,moderate and high doses groups of astragalosideⅣand Ginaton group(positive medicine control group),eight rats each group.After reperfusion for 24 hours,moisture content of brain tissue and the size of cerebral infarction were detected,neurological function score was performed;the expressions of apoptosis-related gene and protein in brain tissue were measured,and the apoptotic conditions of nerve cells was observed.Results:Compared with the model group,neurological function scores lowered notably and neurological function improved obviously,moisture content of brain tissue and the size of cerebral infarction decreased signficantly in moderate and high dose groups of astragaloside Ⅳ(P<0.05);the apoptotic conditions of nerve cells of the rats in low,moderate and high doses groups of astragaloside Ⅳ improved obviously,among them,high dose group of astragalosideⅣthe most outstanding,apoptosis index(AI)of moderate and high doses groups of astragaloside Ⅳdecreased notably(P<0.05);the expressions of Bax mRNAdownregulated distinctly,the expressions of bcl-2 mRNA upregulated,the value of bcl-2/Bax rose apparently(P<0.05),the expressions of caspase-3 and NF-кB protein downre regulated notably(P<0.05).Conclusion:AstragalosideⅣshows the inhibitory effects on nerve cell apoptosis of the rats,which might be related to regulating the expressions of apoptosis-related gene and protein.