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影响及机制研究  

Effect of Mitochondrial ATP-sensitive Potassium Channel Opener on Myocardial Cells in Rats with Coronary Heart Disease and Its Mecha-nism

作　　者：谢玉霞 姜海兵 杨洁 张静 梁铖 刘文宁 Xie Yuxia;Jiang Haibing;Yang Jie(The Second Department of Cardiovascular Medicine,ffiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University,Xinjiang Medical University,Xinjiang 830000,China)

机构地区：[1]新疆维吾尔自治区中医医院心血管二科,乌鲁木齐830000 [2]新疆维吾尔自治区中医医院心血管四科,乌鲁木齐830000

出　　处：《医学研究杂志》2020年第3期65-69,共5页Journal of Medical Research

基　　金：新疆维吾尔自治区自然科学基金资助(2017D01C171)。

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影响及机制.方法将50只SD大鼠随机分为对照组、模型组、二氮嗪低、中、高剂量组,每组10只.除对照组外,其余各组大鼠以高脂饲料喂养6周后,均以30μg/kg的剂量腹腔注射垂体后叶素,每24h注射1次,共3次,构建冠心病大鼠模型,造模后检测血清中肿瘤坏死因子-α(tumor necro-sis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)水平;苏木精-伊红(hematoxylin-eosin,HE)染色观察心肌组织结构变化;原位缺口末端转移酶标记法检测大鼠心肌细胞凋亡;Western blot法检测心肌组织内向整流钾通道6.2亚基(inwardly rectified potassium channel6.2,Kir6.2)和细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)1/2的表达水平.结果冠心病大鼠造模成功,与模型组比较,各给药组大鼠血清炎性细胞因子TNF-α、IL-1β、IL-6显著下降(P<0.05);HE染色结果表明,各给药组大鼠心肌组织结构损伤显著改善;且心肌细胞凋亡数目显著减少(P<0.05);与模型组比较,各给药组Kir6.2表达量显著上升,且呈剂量依赖性,ERK1/2表达量亦显著下降(P<0.05).结论线粒体ATP敏感性钾离子通道开放剂二氮嗪能够对冠心病大鼠起到治疗作用,其机制可能为降低炎性反应,以及通过抑制ERK1/2的表达来缓解心肌细胞凋亡.Objective To investigate the effect and mechanism of mitochondrial ATP-sensitive potassium channel opener on myo-cardial cells in rats with coronary heart disease.Methods Fifty SD rats were randomly divided into control group,model group and di-azoxide low,medium and high dose groups,with 10 rats in each group.Except the control group,the rats in the other groups were fed with high-fat diet for 6 weeks,and the pituitrin was injected intraperitoneally at a dose of 30μg/kg,and injected once every 24 hours for 3 times to construct a rat coronary heart disease model.The serum inflammatory factors TNF-a,IL-1β,IL-6 were detected after the model.Myocardial tissue structure changes were observed by HE staining.Myocardial apoptosis was detected by in situ nick end transfer-ase labeling.Expression levels of Kir6.2 and ERK 1/2 was detected by W estern blot.Results The model of coronary heart disease was successful.Compared with the model group,serum inflammatory factors TNF-a,IL-1β and IL-6 were significantly decreased in each group(P<0.05).HE staining showed that each gave the myocardial tissue damage of the rats in the drug group was improved to some extent,and the number of cardiomyocyte apoptosis was significantly decreased(P<0.05).Compared with the model group,the expres-sion of Kir6.2 in each drug group was significantly increased in a dose-dependent manner.The expression of ERK1/2 was also signifi-cantly decreased(P<0.05).Conclusion The mitochondrial ATP-sensitive potassium channel opener diazoxide can treat coronary heart disease in rats,which may reduce inflammation and inhibit cardiomyocyte apoptosis by inhibiting the expression of ERK1/2.

关 键 词：冠心病 线粒体 ATP敏感性钾离子通道开放剂 凋亡 机制 

分 类 号：R541.4[医药卫生—心血管疾病]