线粒体ATP敏感性钾离子通道开放剂调控冠心病大鼠心肌凋亡的功能及机制  

Function and Mechanism of Mitochondrial ATP-sensitive Potassium Channel Openers Regulating Myocardial Apoptosis in Rats with Coronary Heart Disease

作　　者：贺丹娜[1] 赵瑞平[1] 李帷[1] 杨扬 王栋[1] HE Danna;ZHAO Ruiping;LI Wei;YANG Yang;WANG Dong(Baotou Central Hospital,Baotou 014040,Inner Mongolia,China)

机构地区：[1]包头市中心医院,内蒙古包头014040

出　　处：《中西医结合心脑血管病杂志》2023年第14期2576-2581,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金资助项目(No.81760077);内蒙古自治区自然科学基金项目(No.2021MS08120)。

摘　　要：目的:探讨线粒体ATP敏感性钾离子通道开放剂对冠心病大鼠心肌细胞凋亡的影响及机制。方法:将50只SD大鼠随机分为对照组、冠心病组及二氮嗪低、中、高剂量组,除对照组外,其余各组大鼠均用高脂饮食联合垂体后叶素构建冠心病大鼠模型,造模后二氮嗪低、中、高剂量组大鼠分别灌胃3,5,7 mg/kg的二氮嗪,每日给药1次,共14 d,对照组和冠心病组大鼠灌胃等体积的生理盐水。治疗14 d后,取各组大鼠心肌组织,苏木精-伊红(HE)染色检测心肌损伤,原位缺口末端转移酶标记法(TUNEL)检测心肌细胞凋亡,酶联免疫吸附法(ELISA)检测血清炎性细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)浓度,蛋白免疫印迹法(Western Blot)检测心肌组织中Cleaved-Caspase 3、Bcl-2、Bax、磷酸化蛋白激酶B(p-AKT)、蛋白激酶B(AKT)、磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、磷脂酰肌醇-3-激酶(PI3K)表达。结果:相比于对照组,冠心病组大鼠心肌损伤严重,血清TNF-α、IL-1β、IL-6显著增加,心肌细胞凋亡指数增加,Cleaved-Caspase 3和Bax表达增加,Bcl-2表达、PI3K和AKT磷酸化水平降低(P<0.05)。相比于冠心病组,二氮嗪低、中、高剂量组大鼠心肌损伤均有缓解,TNF-α、IL-1β、IL-6降低,心肌细胞凋亡指数降低,Cleaved-Caspase 3和Bax表达下调,Bcl-2表达、PI3K和AKT磷酸化水平增加(P<0.05)。结论:线粒体ATP敏感性钾离子通道开放剂二氮嗪可缓解冠心病大鼠心肌细胞损伤及凋亡,其机制为激活抗凋亡的PI3K/AKT信号通路。Objective:To explore the effect of mitochondrial ATP-sensitive potassium channel opener on cardiomyocyte apoptosis in rats with coronary heart disease(CHD).Methods:A total of 50 Sprague-Dawley(SD)rats were randomly divided into the control group,the CHD group,and low-,medium-,and high-dose of diazoxide groups resptctively.Except for the control group,the rats in other groups were treated with a high-fat diet combined with pituitary hormone to construct the CHD rat model.After modeling,the rats in the low-dose,medium-dose,and high-dose of diazoxide groups were treated with 3 mg/kg,5 mg/kg,and 7 mg/kg of diazoxide by intragastric administration,respectively,once a day,for a 14 days.The rats in the control and CHD groups were given an equal volume of normal saline intragastrically.After 14 days of treatment,the myocardial tissues of the rats in each group were collected,hematoxylin-eosin(HE)staining was used to detect myocardial injury;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay was used to detect myocardial cell apoptosis;enzyme-linked immunosorbent assay(ELISA)was used to detect serum inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)concentrations;Western Blot was used to detect Cleaved-Caspase 3,Bcl-2,Bax,p-AKT,AKT,p-PI3K,PI3K expression in myocardial tissue.Results:Compared with the control group,the rats in the CHD group showed severe myocardial damage;TNF-α,IL-1β,and IL-6 significantly increased in serum;cardiomyocyte apoptosis index increased;expression of Cleaved-Caspase 3 and Bax increased;expression of Bcl-2,PI3K,and AKT phosphorylation levels decreased(P<0.05).Compared with the CHD group,the rats in the low-,middle-,and high-dose of diazoxide groups the myocardial injury all alleviated;TNF-α,IL-1β,and IL-6 decreased;the apoptosis index of cardiomyocytes decreased;the expression of Cleaved-Caspase 3 and Bax decreased;the expression of Bcl-2,PI3K,and AKT phosphorylation levels increased(P<0.05).Conclusion:Mit

关 键 词：冠心病 线粒体ATP敏感性钾离子通道开放剂 心肌细胞 凋亡 炎性细胞因子 实验研究 

分 类 号：R541.4[医药卫生—心血管疾病]