川芎嗪对大鼠心肌再灌注损伤保护机制的实验研究-东南大学学报医学版

川芎嗪对大鼠心肌再灌注损伤保护机制的实验研究

作者：吕磊¹ 2 孟庆欣¹ 3 徐军¹ 2 宫剑滨¹ 2 承燕¹ 2 江时森¹ 2

单位：1. 南京大学医学院临床学院,江苏南京 210002;
2. 南京军区南京总医院心血管内科, 江苏南京 210002;
3. 南京军区南京总医院超声诊断科,江苏南京 210002

分类号：R-332; R285.5

出版年·卷·期（页码）：2012·31·第四期（410-414）

摘要：

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。

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 high-dose 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.

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