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2019, v.44(23) 5159-5165

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丹蛭降糖胶囊干预糖尿病心肌损伤作用及机制的实验研究
Experimental study on effect and mechanism of Danzhi Jiangtang Capsules on diabetic myocardial injury

施慧;王靓;方朝晖;倪英群;沈安鲁;刘培培;王翔;黄金玲;
SHI Hui;WANG Liang;FANG Zhao-hui;NI Ying-qun;SHEN An-lu;LIU Pei-pei;WANG Xiang;HUANG Jin-ling;Nursing School,Anhui University of Chinese Medicine;School of Integrated Chinese Medicine and Western Medicine,Anhui University of Chinese Medicine;Institute of Integrated Chinese Medicine and Western Medicine,Anhui Academy of Chinese Medicine;the First Clinical Medical College,Anhui University of Chinese Medicine;

摘要(Abstract):

糖尿病心肌病(DCM)是糖尿病主要心血管并发症之一,该研究在丹蛭降糖胶囊临床可有效防治糖尿病及心血管并发症的基础上,采用体内外相结合的实验方法,探讨丹蛭降糖胶囊保护糖尿病诱发心肌损伤的作用及机制。以高能量饲料联合链脲佐菌素制备2型糖尿病模型大鼠,通过血糖、血脂、血流动力学、心脏质量指数、心脏病理形态学等指标检测,观察丹蛭降糖胶囊干预糖尿病心肌损伤的作用,检测心肌组织TLR4,MyD88,NF-κB p65蛋白表达,初步分析其作用机制;制备丹蛭降糖胶囊含药血清,以高糖诱导的大鼠H9c2心肌细胞为研究对象,通过体外干预,探讨TLR4-MyD88-NF-κB信号通路调节高糖诱导心肌细胞损伤的机制及丹蛭降糖胶囊的干预作用。结果显示,丹蛭降糖胶囊干预后,模型大鼠空腹血糖、糖化血红蛋白、总胆固醇、甘油三酯均显著降低(P<0. 01,P<0. 05);心脏质量指数、左心室质量指数、左心室舒张末压,心肌组织TLR4,MyD88,NF-κB p65蛋白表达均显著降低(P<0. 01,P<0. 05),左心室收缩压、左室内压最大收缩率、左室内压最大舒张率显著升高(P<0. 01,P<0. 05),大鼠心肌组织病理学损伤得到显著改善;同时,可显著抑制高糖诱导心肌细胞TLR4,MyD88,NF-κB p65蛋白表达(P<0. 01)。结果表明,丹蛭降糖胶囊可有效防治糖尿病诱导心肌损伤,其作用机制系抑制高糖诱导TLR4/MyD88/NF-κB信号通路过度表达。
Diabetic cardiomyopathy( DCM) is one of the major cardiovascular complications of diabetes mellitus. Based on the clinical efficacy of Danzhi Jiangtang Capsules( DJC) in the prevention and treatment of diabetes and its cardiovascular complications,both in vivo and in vitro methods were adopted to investigate its effect and underlying mechanism of protecting myocardial injury induced by diabetes. The type 2 diabetic rats were prepared by feeding high-energy food combined with streptozotin( STZ) injection,and the effects of DJC were observed by blood sugar,blood lipid,hemodynamic index,cardiac weight index and the change of cardiac pathological morphology. The protein expressions of TLR4,MyD88 and NF-κB p65 in myocardial tissue were detected and the possible mechanism was preliminarily analyzed. Besides this,DJC containing serum was prepared,H9 c2 cardiomyocyte induced by high sugar were studied to investigate the mechanism of TLR4/MyD88/NF-κB signaling pathway regulating cardiomyocyte injury and the therapeutic effect of DJC. The results demonstrated that fasting blood sugar,glycosylated hemoglobin,total cholesterol and glycerol triglyceride were significantly reduced( P<0. 01,P<0. 05). Cardiac weight index,left ventricle weight index,LVEDP and the protein expressions of TLR4,MyD88 and NF-κB p65 were significantly reduced( P<0. 01,P<0. 05). LVSP,+dp/dtmaxand-dp/dtmaxincreased significantly( P<0. 01,P< 0. 05). Moreover,the pathological damage of myocardial tissue in rats improved significantly. Meanwhile,the protein expressions of TLR4,MyD88 and NF-κB p65 in cardiomyocytes induced by high sugar were significantly inhibited( P<0. 01).It showed that DJC were effective in preventing and treating myocardial injury induced by diabetes and its mechanism may be related to the over-expression of TLR4/MyD88/NF-κB signaling pathway induced by high sugar.

关键词(KeyWords): 糖尿病心肌病;动物模型;血清药理学;丹蛭降糖胶囊;TLR4/MyD88/NF-κB信号通路
diabetic cardiomyopathy;animal model;serum pharmacology;Danzhi Jiangtang Capsules;TLR4/MyD88/NF-κB signaling pathway

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金青年基金项目(81603602);; 安徽省教育厅优秀青年人才支持重点项目(gxyqZD2016131);; 安徽省自然科学基金项目(1908085MH267)

作者(Author): 施慧;王靓;方朝晖;倪英群;沈安鲁;刘培培;王翔;黄金玲;
SHI Hui;WANG Liang;FANG Zhao-hui;NI Ying-qun;SHEN An-lu;LIU Pei-pei;WANG Xiang;HUANG Jin-ling;Nursing School,Anhui University of Chinese Medicine;School of Integrated Chinese Medicine and Western Medicine,Anhui University of Chinese Medicine;Institute of Integrated Chinese Medicine and Western Medicine,Anhui Academy of Chinese Medicine;the First Clinical Medical College,Anhui University of Chinese Medicine;

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