刺槐素对大鼠心肌缺血再灌注损伤的保护作用与机制研究

Protective Effect and Mechanism of Acacetin on Myocardial Ischemia Reperfusion Injury in Rats

目的:探讨刺槐素对大鼠心肌缺血再灌注损伤(MIRI)的作用以及可能的作用机制。方法:对24只Sprague-Dawley(SD)大鼠进行随机分组,分为:假手术组、模型组、刺槐素给药组、刺槐素+AG490给药组,每组6只,通过结扎冠状动脉左前降支,缺血30min,再灌注120 min复制心肌缺血再灌注损伤模型。利用氯化三苯基四氮唑测定心肌梗死面积,紫外分光光度计和酶联免疫法检测血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)的活性,蛋白印迹法分别检测心肌组织中Bcl-2、Bax、Stat3和p-Stat3蛋白相对表达水平。结果:与假手术组比较,模型组大鼠血清中CK-MB、LDH活性明显升高(P<0.01),心肌梗死面积百分比显著增加(P<0.01),p-Stat3/Stat3比率、Bcl-2/Bax比率显著下降(P<0.01);与模型组相比,刺槐素给药组中CK-MB、LDH的活性,以及心肌梗死面积百分比显著降低(P<0.01),Bcl-2/Bax比率和p-Stat3/Stat3比率显著提高(P<0.05)。然而在刺槐素+AG490药物组中刺槐素对于受损心肌的保护作用被AG490消除。结论:刺槐素可减轻MIRI大鼠心肌损伤,发挥心肌保护作用,其机制可能与活化Jak2/Stat3信号通路进而抑制心肌细胞凋亡有关。

Objective:To explore the effect of acacetin on myocardial ischemia reperfusion injury in rats and its possible mechanism.Methods:24 SPF rats were randomly divided into sham operation group,model control group,acacetin administration group,acacetin+AG490 group,with 6 rats in each group.Myocardial ischemia reperfusion injury model was induced by 30 minutes coronary occlusion followed by 2 h reperfusion in rats.The myocardial infarct area was measured by triphenyltetrazolium chloride,the activities of CK-MB and LDH in serum were detected by ultraviolet spectrophotometer and enzyme linked immunoassay,and the relative expression levels of Bcl-2,Bax,Stat3 and p-Stat3 proteins in myocardium were investigated by Western blot.Results:Compared with the sham operation group,the activities of CK-MB and LDH in serum rose obviously in the model group(P<0.01),the percentage of myocardial infarction area increased significantly(P<0.01),the ratio of p-Stat3/Stat3 and Bcl-2/Bax decreased notably(P<0.01);Compared with the model group,the activities of CK-MB and LDH,the percentage of myocardial infarction area were significantly decreased(P<0.05),and the ratios of Bcl-2/Bax and p-Stat3/Stat3 were increased significantly in the acacetin treated group.However,the protective effect of acacetin on damaged myocardium was cleared by AG490 in the group of acacetin+AG490.Conclusions:Acacetin could alleviate myocardial damage and exert myocardial protection in MIRI rats,and its mechanism might be related to the inhibition of cardiomyocyte apoptosis by activating Jak2/Stat3 signal pathway.