利多卡因调节线粒体自噬改善心肌缺血再灌注大鼠心功能

Lidocaine improves cardiac function in rats with myocardial ischemia-reperfusion by regulating mitochondrial autophagy

目的 探讨利多卡因调节线粒体自噬改善心肌缺血再灌注大鼠心功能的作用机制。方法 将大鼠随机分为假手术组、模型组、利多卡因组、自噬抑制剂三甲基腺嘌呤(3-MA)组、利多卡因+3-MA组,建立大鼠心肌缺血再灌注损伤模型,超声检测检测大鼠左室功能,观察左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左心射血分数(LVEF)、左室短轴缩短率(FS)变化;TTC染色检测各组大鼠心肌梗死面积;ELISA方法检测各组大鼠血清中CK-MB、cTnI水平;HE染色观察各组大鼠心肌组织病理变化;Western blot检测各组大鼠心肌组织PINK1/Parkin、LC3Ⅱ/Ⅰ、p62、USP30的蛋白表达。结果 与模型组相比,利多卡因组大鼠LVEF%、FS%显著升高,LVEDD、LVESD显著降低,心肌组织病理损伤减轻,心肌梗死面积显著减小,CK-MB、cTnI水平显著降低,PINK1、Parkin、LC3Ⅱ/Ⅰ、USP30蛋白表达水平显著升高,p62蛋白表达水平显著降低。3-MA组大鼠上述各项指标均有所加重,且利多卡因改善心肌缺血再灌注损伤的作用被3-MA削弱或抑制。结论 利多卡因通过调节线粒体自噬改善心肌缺血再灌注大鼠心功能,其作用机制可能与调控Pink1/Parkin信号通路有关。

Objective To investigate the mechanism of lidocaine improving cardiac function by regulating mitochondrial autophagy in rats with myocardial ischemia-reperfusion injury.Methods Rats were randomly divided into sham operation group,model group,lidocaine group,autophagy inhibitor trimethyladenine(3-MA)group,and lidocaine+3-MA group,and the rat model of myocardial ischemia-reperfusion injury was established.The left ventricular function was detected by ultrasound,and the changes of left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(FS)were observed.The myocardial infarct size was detected by TTC staining;the levels of CK-MB and cTnI in serum of rats in each group were detected by ELISA method.The pathological changes of myocardial tissues were observed by HE staining.The protein expressions of PINK1/Parkin,LC3Ⅱ/Ⅰ,p62,and USP30 in myocardial tissues of rats in each group were detected by Western blot.Results Compared with the model group,the LVEF%and FS%of rats in the lidocaine group were significantly increased,LVEDD and LVESD were significantly decreased,the pathological changes of myocardial tissues were alleviated,the myocardial infarct size was significantly reduced,the levels of CK-MB and cTnl were significantly decreased,the protein expressions of PINK1,Parkin,LC3Ⅱ/Ⅰand USP30 were significantly increased,and the protein expression of p62 was significantly decreased.The above indexes were aggravated in the 3-MA group,and the effect of lidocaine on improving myocardial ischemia-reperfusion injury was weakened or inhibited by 3-MA.Conclusion Lidocaine improves cardiac function in rats with myocardial ischemia-reperfusion by regulating mitochondrial autophagy,and its mechanism may be related to the regulation of Pink1/Parkin signaling pathway.