大豆异黄酮改善糖尿病心肌病大鼠心功能及心肌纤维化机制的研究  

Study on the effects of soy isoflavone on cardiac function and fibrosis in rats with diabetic cardiomyopathy and its mechanisms

作　　者：黄泓轲[1] 罗健玮[2] 冉华 HUANG Hongke;LUO Jianwei;RAN Hua(Department of Pharmacy,Leshan Vocational and Technical College,Leshan 614000,China)

机构地区：[1]乐山职业技术学院药学系,614000 [2]乐山职业技术学院医学系,614000 [3]重庆市黔江中心医院心内科

出　　处：《中国糖尿病杂志》2023年第5期376-381,共6页Chinese Journal of Diabetes

基　　金：2020年乐山市科技计划项目(20SZD050)。

摘　　要：目的 探讨大豆异黄酮对糖尿病心肌病(DCM)大鼠心功能及纤维化的影响机制。方法 60只SD大鼠随机分为正常对照(Con)组、模型组(Mod组)、依那普利组(Ena组)、大豆异黄酮组90 mg/kg组(Soy-iso 90组)、大豆异黄酮180 mg/kg组(Soy-iso 180组)、大豆异黄酮360 mg/kg组(Soy-iso 360组),每组各10只。干预8周后比较各组体重和FPG,检测左室射血分数(EF)、左心室收缩百分率(FS)、左心室后壁厚度(LVPW)、左心室舒张末内径(LVDD)、左心室收缩末内径(LVESD),HE染色观察心肌病理改变,Western blot法检测胶原蛋白I(Collagen Ⅰ)、Collagen Ⅱ、基质金属蛋白酶2(MMP-2)、TGF-β、磷酸化Smad2(p-Smad2)、核红细胞2相关因子2(Nrf2)、血红素氧化酶1(HO-1)蛋白表达。结果 与Con组比较,Mod组体重、EF、FS、p-Nrf2/Nrf2、HO-1蛋白表达降低(P<0.05),FPG、LVPW、LVDD、LVESD和Collagen Ⅰ、Collagen Ⅱ、MMP-2、TGF-β、p-Smad2蛋白表达升高(P<0.05)。与Mod组比较,Soy-iso 180、Soy-iso 360、Ena组体重、EF、FS和p-Nrf2/Nrf2、HO-1蛋白表达升高(P<0.05),FPG、LVPW、LVDD、LVESD和Collagen Ⅰ、Collagen Ⅱ、MMP-2、TGF-β、p-Smad2蛋白表达降低(P<0.05)。结论 大豆异黄酮改善DCM心肌损伤和纤维化,可能与激活Nrf2/HO-1信号通路及抗氧化酶系统活性相关。Objective To explore the effects of soy isoflavone on cardiac function and fibrosis in rats with diabetic cardiomyopathy(DCM)and its mechanisms.Methods SD rats were randomly divided into normal control group(Con),model group(Mod),enalapril group(Ena),soy isoflavone 90 mg/kg group(Soy-iso 90),soy isoflavone 180 mg/kg group(Soy-iso 180)and soy isoflavone 360 mg/kg group(Soy-iso 360).After 8 weeks of intervention,body weight and FPG were compared among the groups.The left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular posterior wall thickness(LVPW),left ventricular end-diastolic diameter(LVDD)and left ventricular end-systolic diameter(LVESD)were detected.The pathological changes of myocardium were observed by HE staining.The expressions of collagen I(Collagen I),Collagen II,matrix metalloproteinase 2(MMP-2),transforming growth factorβ(TGF-β),phosphorylated Smad2(p-Smad2),nuclear erythrocyte 2 related factor 2(Nrf2)and heme oxidase 1(HO-1)proteins were detected by Westerm blot.Results Compared with Con group,body weight,EF,FS,p-Nrf2/Nrf2 and HO-1 proteins were decreased(P<0.05),while FPG,LVPW,LVDD,LVESD and expressions of Collagen I,Collagen II,MMP-2,TGF-βand p-Smad2 proteins were increased in Mod group(P<0.05).Compared with Mod group,body weight,EF,FS,p-Nrf2/Nrf2 and HO-1 proteins were increased(P<0.05),while FPG,LVPW,LVDD,LVESD and expressions of Collagen I,Collagen II,MMP-2,TGF-βand p-Smad2 proteins were decreased in Ena group,Soy-iso 180 group and Soy-iso 360 group(P<0.05.)C.onclusion Soy isoflavone can improve myocardial injury and fibrosis in DCM,which may be related to activating Nrf2/HO-1 signaling pathways and activity of antioxidant enzyme system.

关 键 词：糖尿病心肌病 大豆异黄酮 核红细胞2相关因子2 血红素氧化酶 信号通路 氧化损伤 纤维化 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]