南方医科大学学报2016，Vol.36Issue(12)：1706-1711,6.DOI:10.3969/j.issn.1673-4254.2016.12.20
Rho激酶和自噬在法舒地尔抗心肌缺血/再灌注损伤中的作用
Role of autophagy in fasudil-induced Rho kinase inhibition for protection against myocardial ischemia-reperfusion injury in rats
摘要
Abstract
Objective To investigate the changes of autophagy in ischemic myocardium of rats treated with fasudil for inhibiting Rho kinase.Methods The hearts isolated from male Sprague-Dawley rats were subjected to 30 min of occlusion of the left anterior descending artery followed by 120 min of reperfusion with or without treatment with fasudil or fasudil+Wort.The left ventricular hemodynamics were continuously recorded,and the coronary effluent was collected during the reperfusion to determine lactate dehydrogenase (LDH) levels.The mRNA expressions of autophagy-related genes Atg5 and Beclin1 and apoptosis-related genes bax and bcl-2 were detected by RT-PCR,and the protein expression of caspase-3 was detected by Western blotting.Results Compared with I/R group,fasudil significantly improved the left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure and rate pressure product,reduced LDH release during reperfusion,increased Atg5 and Beclin1 mRNA expression and the ratio of Bcl-2/Bax,and lowered caspase 3 protein expression.The autophagy inhibitor Wort significantly attenuated the effect of fasudil in the rat hearts.Conclusion Fasudil treatment for inhibiting Rho kinase promoted autophagy in ex vivo rat heart to protect against myocardial ischima-reperfusion injury possibly by reducing apoptosis of the cardiac myocytes.关键词
心脏/缺血/再灌注损伤/自噬/法舒地尔/渥曼青霉素Key words
hearts/ischemia/reperfusion injury/autophagy/fasudil/wortmannin引用本文复制引用
叶红伟,方婷婷,谷小雨,王娅,朱广宇,于影,高琴..Rho激酶和自噬在法舒地尔抗心肌缺血/再灌注损伤中的作用[J].南方医科大学学报,2016,36(12):1706-1711,6.基金项目
安徽省自然科学基金(1508085MH169,1508085QH150) （1508085MH169,1508085QH150）
蚌埠医学院校级科研项目(byky1311) （byky1311）
安徽省大学生创新创业训练项目(201510367019) （201510367019）
