金雀异黄酮对糖尿病大鼠心肌Nrf2/HO-1通路的影响  

Effects of genistein on Nrf2/HO-1 pathway in myocardial tissues of diabetic rats

作　　者：贾强[1] 王元元[2] 刘小粉[1] 马善峰[1] 杨锐[1] JIA Qiang;WANG Yuanyuan;LIU Xiaofen;MA Shanfeng;YANG Rui(Department of Physiology,Bengbu Medical College,Bengbu Anhui 233030,China;Center of Functional Experiment,Bengbu Medical College,Bengbu Anhui 233030,China)

机构地区：[1]蚌埠医学院生理学教研室,安徽蚌埠233030 [2]蚌埠医学院机能实验中心,安徽蚌埠233030

出　　处：《中南大学学报（医学版）》2019年第8期850-856,共7页Journal of Central South University ：Medical Science

基　　金：安徽省高校自然科学研究项目(KJ2018A0994);安徽省大学生创新创业训练项目(201810367022,201810367054);蚌埠医学院科研项目(BYKF1706)~~

摘　　要：目的:观察金雀异黄酮(genistein,Gen)对糖尿病大鼠心肌组织核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)/血红素氧化酶1(heme oxygenase-1,HO-1)通路的影响。方法:将32只雄性SD大鼠随机分为4组:正常对照(NC)组、糖尿病对照(DM)组、低剂量Gen治疗(L-Gen)组和高剂量Gen治疗(H-Gen)组(n=8)。采用腹腔注射55mg/kg链脲佐菌素建立糖尿病大鼠模型。造模成功后,L-Gen组和H-Gen组大鼠分别灌胃给予Gen溶液10和50 mg/kg。8周后,测定各组大鼠左心室动力学指标和空腹血糖(fasting blood glucose,FBG)水平;测定心肌组织丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)水平;采用透射电镜观察心肌超微结构变化;RT-PCR检测心肌组织HO-1 mRNA表达,蛋白质印迹法检测Nrf2和HO-1蛋白表达。结果:与NC组比较,DM组左心室收缩压(left ventricular systolic pressure,LVSP),左心室内压最大上升/下降速率(maximal rise/fall rate of left ventricular pressure,±dp/dtmax),GSH-Px,SOD和CAT水平明显降低(均P<0.01);左心室舒张末期压(left ventricular end-diastolic pressure,LVEDP),FBG和MDA水平明显增高(均P<0.01);心肌超微结构损伤明显,心肌组织Nrf2和HO-1表达明显降低(均P<0.01)。与DM组比较,L-Gen组FBG无显著差异,±dp/dtmax和LVSP明显升高(均P<0.05),LVEDP和MDA水平明显下降(P<0.05或P<0.01),GSH-Px,SOD和CAT活性明显增高(P<0.05或P<0.01),心肌超微结构损伤减轻,Nrf2和HO-1表达升高(均P<0.01);H-Gen组上述指标改善更明显(P<0.05或P<0.01)。结论:金雀异黄酮可减轻糖尿病大鼠心肌氧化应激损伤,其机制与调节心肌Nrf2/HO-1通路,提高抗氧化酶活性相关。Objective: To investigate the effects of genistein (Gen) on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in myocardial tissues of diabetic rats. Methods: Thirty-two male SD rats were randomly divided into 4 groups: a normal control (NC) group,a diabetic control (DM) group,a low-dose Gen treatment (L-Gen) group,and a high-dose Gen treatment (H-Gen) group (n=8).Intraperitoneal injection of streptozotocin was utilized to induce diabetic rat model.After the establishment of diabetic model,the rats in L-Gen and H-Gen groups were intragastric administration with 10 and 50 mg/kg Gen solution.Following 8 weeks,the left ventricular hemodynamic parameters and fasting blood glucose (FBG) levels were measured.The levels of malondialdehyde (MDA),glutathione peroxidase (GSH-Px),superoxide dismutase (SOD) and catalase (CAT) in myocardial tissue were determined.The ultrastructure of myocardium was observed under transmission electron microscopy.The expression of HO-1 at mRNA level in myocardial tissue was detected by RT-PCR.The protein levels of Nrf2 and HO-1 in myocardial tissue were detected by Western blotting. Results: Compared with the NC group,left ventricular systolic pressure (LVSP),maximal rise/ fall rate of left ventricular pressure (±dp/dtmax),and the levels of GSH-Px,SOD and CAT were decreased (all P<0.01),while the left ventricular end-diastolic pressure (LVEDP),FBG and MDA were increased (all P<0.01) in the DM group.The myocardial ultrastructure was obviously damaged,and the expressions of myocardial Nrf2 and HO-1 were significantly decreased (both P<0.01) in the DM group.Compared with the DM group,there was no difference in FBG in the L-Gen group,while ±dp/dtmax and LVSP were significantly increased (all P<0.05),and LVEDP and MDA were decreased (P<0.05 or P<0.01),and the levels of GSH-Px,SOD and CAT were increased (P<0.05 or P<0.01) in the L-Gen group.The myocardial ultrastructure damage was alleviated and the expressions of Nrf2 and HO-1 were increased (both P<0.01) in the

关 键 词：金雀异黄酮 糖尿病 心肌组织 核因子E2相关因子2/血红素氧化酶1通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]