依那普利减轻肢体缺血-再灌注模型大鼠心肌损伤的作用机制  

Mechanism by which enalapril alleviates myocardial injury in a rat model of limb ischemia-reperfusion

作　　者：邢宏昶[1] 曹建平[1] 朱静[1] 姚鲲[2] Xing Hongchang;Cao Jianping;Zhu Jing;Yao Kun(Department of Anesthesiology,Central Hospital of Shenyang Medical College,Shenyang 110024,Liaoning Province,China;Department of Hematology,Shengjing Hospital Affiliated to China Medical University,Shenyang 110021,Liaoning Province,Chin)

机构地区：[1]沈阳医学院附属中心医院麻醉科,辽宁省沈阳市110024 [2]中国医科大学附属盛京医院血液科,辽宁省沈阳市110021

出　　处：《中国组织工程研究》2022年第11期1747-1751,共5页Chinese Journal of Tissue Engineering Research

基　　金：辽宁省自然科学基金项目(2019-ZD-0325),项目负责人:邢宏昶;沈阳医学院科学基金项目(20181029),项目负责人:邢宏昶。

摘　　要：背景:有研究证实依那普利可以减轻肢体缺血再灌注导致的心肌损伤,但对其作用机制的研究还没有报道。目的:探讨依那普利减轻大鼠肢体缺血-再灌注心肌损伤的作用机制。方法:健康成年雄性SD大鼠48只随机分为对照组、模型组、依那普利组和抑制剂组。除对照组外,其余各组采用橡皮带环绕结扎大鼠双后肢根部3 h、再灌注3 h制备肢体缺血再灌注模型;抑制剂组再灌注前30 min时静脉注射PI3K抑制剂LY2940020.3 mg/kg,依那普利组和抑制剂组再灌注即刻开始静脉输注依那普利13μg/(kg·h)至再灌注结束;其余两组再灌注即刻开始给予等量生理盐水溶液。再灌注3 h时麻醉下处死大鼠,取心肌组织,检测心肌组织病理学改变、心肌组织细胞凋亡指数及凋亡基因表达、细胞传导通路蛋白表达。实验方案由沈阳医学院实验动物伦理委员会于2019年10月批准,批准号:研伦审第(2019)85号。结果与结论:(1)光镜下与模型组比较,依那普利组心肌组织病理学损伤减轻;与依那普利组比较,抑制剂组心肌组织病理学损伤加重;(2)与模型组比较,依那普利组心肌组织细胞凋亡指数降低,Bax蛋白表达下调,PI3K、p-Akt和Bcl-2蛋白表达上调(P<0.05);(3)与依那普利组比较,抑制剂组心肌组织细胞凋亡指数升高,Bax蛋白表达上调,PI3K、p-Akt和Bcl-2蛋白表达下调(P<0.05);(4)结果说明,依那普利可通过激活PI3K/Akt信号通路,抑制细胞凋亡,减轻大鼠肢体缺血-再灌注心肌损伤。BACKGROUND:Studies have confirmed that enalapril can alleviate myocardial injury caused by limb ischemia-reperfusion,but the mechanism of its action has not been reported.OBJECTIVE:To investigate the effect mechanism of enalapril reduction of myocardial injury by ischemia-reperfusion in the rat limb.METHODS:Forty-eight healthy adult male Sprague-Dawley rats were randomly divided into control group,model group,enalapril group and inhibitor group.Except for the normal control group,rats were bundled around the ligation of the posterior limbs with a rubber band for 3 hours,followed by 3-hour reperfusion to establish the model of limb ischemia-reperfusion.Intravenous injection of 0.3 mg/kg LY294002 was given in the inhibitor group 30 minutes before reperfusion.Enalapril group and inhibitor group were given intravenous infusion of enalapril 13μg/kg/h immediately after reperfusion until the end of reperfusion.An equal amount of normal saline solution was given in the other two groups immediately after reperfusion.After 3 hours of reperfusion,the rats were killed and the myocardial tissue was taken.Myocardial histopathological changes,apoptotic index,apoptosis gene expression and cell conduction pathway protein expression were detected.The study was approved by the Laboratory Animal Ethical Committee of Shenyang Medical College in October 2019 with an approval No.(2019)85.RESULTS AND CONCLUSION:Compared with the model group,myocardial histopathological injury was reduced in the enalapril group.Compared with the enalapril group,myocardial histopathological injury was aggravated in the inhibitor group.Compared with the model group,myocardial apoptosis index(AI)was decreased,Bax expression was downregulated,PI3 K,p-Akt and Bcl-2 expression was up-regulated in the enalapril group(P<0.05).Compared with the enalapril group,myocardial apoptosis index was increased,Bax expression was up-regulated,PI3 K,p-Akt and Bcl-2 expression was downregulated in the inhibitor group(P<0.05).The mechanism by which enalapril reduces limb isch

关 键 词：依那普利 再灌注损伤 心肌 1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 细胞凋亡 炎症 氧化应激 

分 类 号：R446[医药卫生—诊断学] R496[医药卫生—临床医学]