二氢杨梅素通过抑制HMGB1改善糖尿病大鼠心功能不全

Dihydromyricetin improves cardiac insufficiency by inhibiting HMGB1 in diabetic rats

目的探讨二氢杨梅素(DHM)对糖尿病大鼠心功能不全的影响及其作用机制。方法24只SPF级雄性SD大鼠随机等分为正常对照组(Control组,n=6)、2型糖尿病组[T2DM组,n=6,高糖高脂饲料喂养6周加小剂量链脲佐菌素(STZ)]、二甲双胍组(MET组,n=6,构建T2DM模型大鼠后,给予MET 150 mg/kg灌胃8周)、二氢杨梅素组(DHM组,n=6,构建T2DM模型大鼠后,给予DHM 250mg/kg灌胃8周)。检测各组大鼠空腹血糖、低密度脂蛋白(LDL-C)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)及糖化血红蛋白(HbA1c)含量,ELISA法检测血浆中胰岛素、高迁移率族蛋白-1(HMGB1)的含量,心脏彩色超声仪检测大鼠心功能,生物信号采集系统测定大鼠心电图,HE染色观察大鼠心肌组织形态,Westernblot法检测大鼠心肌组织HMGB1、NF-κB p65、磷酸化NF-κB p65(p-NF-κB p65)蛋白的表达水平。结果与Control组比较,T2DM组造模后出现心律失常,心率减慢,左室射血分数(EF)、左室短轴缩短率(FS)、每搏输出量(SV)显著下降(P<0.05或0.01),大鼠的心室舒张末期内径(LVIDd)、左心室收缩期内径(LVIDs)、心脏肥厚指数、血浆中HMGB1的含量、心肌组织中的HMGB1、NF-κB p65磷酸化蛋白表达水平显著升高(P<0.05或0.01);与T2DM组比较,DHM组能显著改善大鼠各项心功能指标(P<0.05或0.01),并且能显著降低血浆中HMGB1的含量、下调心肌组织中的HMGB1及NF-κB p65磷酸化蛋白的表达(P<0.05或0.01)。结论DHM改善糖尿病大鼠心功能可能与下调HMGB1表达及抑制NF-κB p65磷酸化有关。

Objective To investigate the effect of dihydromyricetin(DHM)on cardiac insufficiency in diabetic rats and explore the underlying mechanism.Method Twenty-four male SD rats were randomized equally into normal control group,type 2 diabetes(T2DM)group fed on a high-glucose and high-fat diet for 6 weeks with low-dose streptozotocin(STZ)injection,metformin(MET)group with daily intragastric administration of MET(150 mg/kg)for 8 weeks after T2DM modeling,and dihydromyricetin(DHM)group with daily intragastric administration of DHM(250 mg/kg)for 8 weeks after modeling.The levels of fasting blood glucose,low density lipoprotein(LDL-C),triglyceride(TG),total cholesterol(TC),high density lipoprotein(HDL-C)and glycosylated hemoglobin(HbA1c)of the rats were measured,and plasma levels of insulin and high mobility group protein-1(HMGB1)were detected with ELISA.The cardiac function of the rats was assessed using color echocardiography,ECG was measured using a biological signal acquisition system,and myocardial pathology was observed with HE staining.The protein expressions of HMGB1,nuclear factor-κB(NF-κB)p65 and phospho-NF-κB p65(p-NF-κB p65)in the myocardial tissue were detected using Western blotting.Results Compared with the control group,the rats in T2DM group showed significant anomalies in cardiac function after modeling with significantly increased plasma HMGB1 level and expressions of HMGB1,NF-κB p65 and p-NF-κB p65 proteins in the myocardial tissue(P<0.05 or 0.01).Treatment with DHM significantly improved the indexes of cardiac function of the diabetic rats(P<0.05 or 0.01),decreased plasma HMGB1 level and down-regulated the protein expressions of HMGB1 and p-NF-κB p65 in the myocardial tissue(P<0.05 or 0.01).Conclusion DHM treatment can improve cardiac function in diabetic rats possibly by down-regulation of HMGB1 and phospho-NF-κB p65 expressions in the myocardium.