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阿托伐他汀通过增加连接蛋白CX43表达保护心肌免受缺血再灌注心律失常
贵州医科大学 麻醉与心脏电生理课题组
翻译：王璐 编辑：王婷婷 审校：曹莹
目的：研究阿托伐他汀是否能够通过激活磷脂酰肌醇-3-激酶 (PI3K)/Akt 通路和线粒体 ATP 敏感性钾来增强连接蛋白 43 (Cx43) 的表达，从而防止心肌缺血再灌注损伤。
方法：在离体大鼠心脏灌流前降支（LAD）缺血30 min后，分别给予经典缺血后处理（IPOST）、阿托伐他汀、阿托伐他汀联合PI 3 K和KATP通道抑制剂，然后再灌注120 min，观察QRS时限和缺血再灌注室性心律失常的发生情况。测定乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB）水平，并通过免疫印迹和免疫组化评估Cx43表达。
结果：再灌注120 min后，阿托伐他汀和IPOST可显著缩短QRS时限，抑制室性心律失常。降低LDH、CK-MB水平。同时，阿托伐他汀和IPOST也显著增强了Cx43的表达和Cx43的磷酸化。
结论：这种保护作用在PI 3 K抑制剂或线粒体KATP通道抑制剂的存在下消除，提示阿托伐他汀通过激活PI 3 K/Akt信号通路和线粒体KATP通道，对心肌缺血再灌注损伤具有保护作用。
原始文献来源
Bo Bian(MD), Xuefang Yu(MD)*, Qing Wang(MM) ,et,al.Atorvastatin protects myocardium against ischemia-reperfusion arrhythmia by increasing Connexin 43 expression: A rat model[J].European Journal of Pharmacology.2015.09.23;http://dx.doi.org/10.1016/j.ejphar.
AbstractAtorvastatin protects myocardium against ischemia-reperfusion arrhythmia by increasing Connexin 43 expression: A rat model
Background: his study was designed to investigate whether atorvastatin is able to protect against myocardial ischemia-reperfusion injury by enhancing the expression of Connexin 43 (Cx43) via the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and mitochondrial ATP-sensitive potassium (KATP) channels.
Method: Isolated perfused rat hearts were treated with classic ischemia postconditioning (IPOST), atorvastatin, and atorvastatin combined with inhibitor of PI3K and KATP channels, respectively, after 30 min of LAD ischemia and then subjected to reperfusion for 120 min. The QRS duration and the ischemia-reperfusion ventricular arrhythmia were assessed. The lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels were measured and the Cx43 expression was assessed by immunoblotting and immunohistochemistry.
Results: After 120min of reperfusion, atorvastatinand IPOST significantly decreased the QRS duration and inhibited ventricular arrhythmia. They also decreased the levels of LDH and CK-MB. Meanwhile, atorvastatin and IPOST also significantly enhanced the Cx43 expression and the phosphorylation of Cx43.
Conclusion: such protective effects were abolished in the presence of the inhibitor of PI3K or the inhibitor of mitochondrial KATP channels. This study suggests that atorvastatin protected against myocardial ischemia-reperfusion injury and enhanced the expression of Cx43 by activating the PI3K/Akt pathway and mitochondrial KATP channels.
