阿魏酸川芎嗪对缺血再灌注大鼠心肌细胞凋亡及凋亡相关蛋白表达的影响

Effects of ligustrazine ferulate on myocardial apoptosis and apoptosis-related protein expression in rats with myocardial ischemia-reperfusion injury

目的:观察阿魏酸川芎嗪对缺血再灌注损伤大鼠心肌细胞凋亡的影响,并探讨其可能机制。方法:将60只雄性SD大鼠随机分成5组:(1)假手术组;(2)缺血再灌注组;(3)川芎嗪(4 mg/kg)组;(4)阿魏酸川芎嗪低剂量(4 mg/kg)组;(5)阿魏酸川芎嗪高剂量(8 mg/kg)组。采用结扎左冠状动脉前降支30 min、再灌注120min的方法复制大鼠心肌缺血再灌注模型;各组大鼠于再灌注前10 min分别颈静脉注射给药,于再灌注结束后,进行血清生化及心肌组织学检测。结果:阿魏酸川芎嗪能显著降低心肌缺血再灌注损伤大鼠血清中肌酸激酶同功酶、乳酸脱氢酶、心肌钙蛋白I和丙二醛的水平,提高总超氧化物歧化酶活性,增加心肌Bcl-2蛋白的表达,减少心肌Bax蛋白的表达,提高Bcl-2/Bax的比值和降低心肌细胞凋亡指数,与缺血再灌注组比较,差异有统计学意义(P<0.01)。阿魏酸川芎嗪各项指标优于川芎嗪(P<0.05或P<0.01)。结论:阿魏酸川芎嗪能减轻大鼠心肌缺血再灌注损伤;其抗缺血再灌注诱导的心肌细胞凋亡的机制可能与其上调Bcl-2蛋白和下调Bax蛋白表达有关。

AIM： To observe the effects of ligustrazine ferulate on the apoptosis of myocardial cells in rats with myocardial ischemia-reperfusion injury, and to explore its possible mechanism. METItOI~： Sixty male SD rats were ran- domly divided into five groups： sham-operation group, ischemia-reperfusion group, ligustrazine （4 mg/kg） group, low-dose （4 mg/kg） ligustrazine ferulate group and high-dose （8 mg/kg） ligustrazine ferulate group. The rat myocardial ischemia- reperfusion model was established by 30 min of myocardial ischemia followed by 120 min of reperfusian. Drugs were adminis- tered to the rats by jugular vein injection 10 rain before reperfusion. After the reperfusion was finished, the biochemical indi- cators in serum and the histological indexes in myocardium were detected. RESULTS： Compared with ischemia-reperfusion group, ligustrazine ferulate lowered the serum levels of creatine kinase MB form, lactate dehydrogenase, cardiac troponin I and malondialdehyde, elevated the activity of total superoxide dismutase in serum and the expression of Bcl-2 protein in my- ocardium, decreased the expression of Bax protein and myocardial apoptotic index, and increased the Bcl-2/Bax ratio （all P 〈0.01 ）. All the indicators in ligustrazine ferulate groups were dose-dependently superior to those in ligustrazine group （ P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Ligustrazine ferulate protects rats against myocardial ischemia-reperfusion inju- ry. Its anti-apoptotic effect may be related to up-regulation of Bcl-2 and down-regulation of Bax.