糖原合酶激酶-3β在川芎嗪对心肌缺血再灌注损伤保护中的作用-东南大学学报医学版

糖原合酶激酶-3β在川芎嗪对心肌缺血再灌注损伤保护中的作用

单位：南京军区南京总医院干部心内科, 江苏南京 210002

分类号：R331.31;R33-33

出版年·卷·期（页码）：2016·35·第六期（836-840）

摘要：

目的：探讨川芎嗪对在体大鼠缺血再灌注（IR）损伤心肌的影响以及糖原合酶激酶-3β（GSK-3β）在其中的作用。方法：40只雄性SD大鼠随机分为假手术组、IR对照组、川芎嗪组、川芎嗪+渥曼青霉素组以及渥曼青霉素组，每组8只。假手术组冠状动脉左前降支不结扎，余各组均结扎左前降支，松结后直接再灌注。再灌注末，测定血浆心肌酶水平及缺血心肌组织腺嘌呤核苷三磷酸（ATP）含量，采用电子显微镜观察缺血心肌超微结构变化，蛋白质印迹法测定缺血心肌组织磷酸化Akt（p-Akt）和磷酸化GSK-3β（p-GSK-3β）的蛋白表达水平。结果：IR对照组血浆心肌酶升高，缺血心肌组织ATP含量减少，线粒体损伤。川芎嗪组心肌酶释放减少，ATP含量增加，心肌细胞线粒体超微结构损伤明显减轻，p-Akt和p-GSK-3β水平显著增高。渥曼青霉素减弱了川芎嗪对IR心肌的保护作用并抑制了川芎嗪所致的p-Akt和p-GSK-3β蛋白水平的增加。结论：川芎嗪预处理能减少在体大鼠心肌IR所致心肌酶释放和ATP下降，减轻线粒体损伤，PI3K/Akt-GSK-3β信号通路参与介导该保护作用。

Objective: To observe the effect of ligustrazine(tetramethylpyrazine,TMP) on myocardial ischemia reperfusion(IR) and to discuss the role of glycogen synthase kinase 3β(GSK-3β) in a rat IR model in vivo. Methods: Forty male SD rats were randomly divided into Sham,IR control,TMP,TMP+Wortmannin(wort) and Wort group.The left anterior descending artery(LAD) was not ligated in the Sham group.LAD in other groups was ligated for 35 min followed by 120 min of reperfusion.The activities of creatine kinase MB fraction(CK-MB) and lactate dehydrogenase(LDH) and the content of myocardial ATP were measured at the end of reperfusion.Electron microscopic evaluation was conducted.Expression of phosphorylated Akt and phosphorylated GSK-3β were detected by Western blot.Results: The level of plasma CK-MB and LDH increased and ATP content decreased in the IR control group while the mitochondria were damaged.Compared to the IR control group,pretreatment with TMP markedly decreased plasma CK-MB and LDH,increased ATP content,attenuated mitochondrial injury,and induced Akt and GSK-3β phosphorylation.However,wortmannin attenuated the TMP-induced phosphorylation of Akt and GSK-3β and abolished the cardioprotective effect of TMP. Conclusion: Ligustrazine pretreatment attenuates myocardial IR injury and mitochondrial injury through decreasing the myocardial enzyme release and boosting ATP level.This cardioprotective effect of ligustrazine is mediated through activating the PI3K/Akt-GSK-3β signal transduction pathway.

参考文献：

[1] CHI H J CHEN M L YANG X C et al.Progress in therapies for myocardial ischemia reperfusion injury[J].Curr Drug Targets,2016[Epub ahead of print].
[2] MIURA T,TANNO M.Mitochondria and GSK-3beta in cardioprotection against ischemia/reperfusion injury[J].Cardiovasc Drugs Ther,2010,24(3):255-263.
[3] QIAN W,XIONG X,FANG Z,et al.Protective effect of tetramethylpyrazine on myocardial ischemia-reperfusion injury[J].Evid Based Complement Alternat Med,2014,2014:107501.
[4] TAN F,FU W,CHENG N,et al.Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion[J].Exp Ther Med,2015,9(5):1757-1762.
[5] 吕磊,孟庆欣,徐军,等.川芎嗪对大鼠心肌再灌注损伤保护机制的实验研究[J].东南大学学报:医学版,2012,31(4):410-414.
[6] FINKEL T,MENAZZA S,HOLMSTROM K M,et al.The ins and outs of mitochondrial calcium[J].Circ Res,2015,116(11):1810-1819.
[7] 丁士骜,梅举.线粒体与心肌缺血/再灌注损伤的研究进展[J].医学综述,2016,22(1):37-41.
[8] SKYSCHALLY A,GENT S,AMANAKIS G,et al.Across-species transfer of protection by remote ischemic preconditioning with species-specific myocardial signal transduction by reperfusion injury salvage kinase and survival activating factor enhancement pathways[J].Circ Res,2015,117(3):279-288.
[9] YAO H,HAN X.The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway[J].Am J Cardiovasc Drugs,2014,14(6):433-442.
[10] 吕磊,徐军.心肌缺血再灌注损伤中线粒体保护的研究进展[J].东南大学学报:医学版,2015,34(1):131-134.
[11] MIURA T,TANNO M,SATO T.Mitochondrial kinase signalling pathways in myocardial protection from ischaemia/reperfusion-induced necrosis[J].Cardiovasc Research,2010,88(1):7-15.
[12] WU Q L,SHEN T,SHAO L L,et al.Ischemic postconditioning mediates cardioprotection via PI3K/GSK-3β/β-catenin signaling pathway in ischemic rat myocardium[J].Shock 2012,38(2):165-169.

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