川芎嗪对大鼠心肌再灌注损伤保护机制的实验研究

目的:观察川芎嗪对大鼠心肌缺血再灌注(IR)损伤的保护作用以及其作用机制。方法:建立在体大鼠心肌IR模型,随机分为假手术组,IR组,川芎嗪低、中、高剂量组以及川芎嗪+渥曼青霉素组。测定血浆肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平,心肌梗死面积,缺血心肌组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,Western blotting法检测心肌磷酸化蛋白激酶B(Akt)、磷酸化内皮型一氧化氮合酶(eNOS)的表达。结果:与IR组相比,川芎嗪中、高剂量组的血浆CK-MB和LDH水平降低,心肌组织MDA含量减少,SOD活性增加,心肌梗死面积减小,Akt磷酸化水平增高,川芎嗪各组eNOS磷酸化水平均增高。渥曼青霉素显著抑制川芎嗪所致的Akt和eNOS磷酸化,并能消除川芎嗪的心肌保护作用。结论:川芎嗪预处理能减少大鼠心肌缺血再灌注损伤且与剂量相关,其通过磷脂酰肌醇-3激酶(PI3K)/Akt-eNOS信号通路保护在体大鼠再灌注损伤心肌。

Study of protective mechanism of ligustrazine on myocardial ischemia reperfusion injury in rats

Objective:The effect of ligustrazine(tetramethylpyrazine,TMP) on myocardial ischemia reperfusion(IR) and the mechanism of protection were investigated in a rat IR model.Methods: Rat heart IR model was established in vivo.Sprague-Dawley rats were randomly divided into sham,IR control,low-,middle-and highdose of TMP pretreated,and TMP + wortmannin group.The activities of creatine kinase MB fraction(CK-MB) and lactate dehydrogenase(LDH),infarct size as well as myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) content were measured.Expression of phosphorylated Akt and endothelial nitric oxide synthase(eNOS) were detected by Western blotting.Results: Compared to the IR group,pretreatment with middle and high does of TMP markedly inhibited increases in plasma CK-MB and LDH,decreased MDA content and increased SOD activity,decreased infarct size and induced Akt phosphorylation.In all three TMP-pretreatment groups,the level of eNOS phosphorylation increased.However,wortmannin eliminated the TMP-induced phosphorylation of Akt and eNOS and abolished the cardioprotective effect of TMP.Conclusion: Ligustrazine attenuated myocardial IR injury in a dose-related manner.The cardioprotective effect of ligustrazine was mediated through PI3K / Akt-eNOS signal transduction pathway.