小檗碱对糖尿病早期心肌病大鼠保护及其机制研究

The Protective Effect and Mechanism of Borberine for Early Diabetic Cardiomyopathy Rats

目的:探讨小檗碱对早期糖尿病心肌病的作用及机制。方法:雄性SD大鼠随机分为E组(对照组,n=8)、A组(糖尿病组)、C组(小檗碱组,n=8)、B组(福辛普利组n=8)、D组(联合用药组n=8),后四组一次腹腔注射链脲佐菌素STZ(45mg/kg)建立糖尿病模型,造模后4周,C组大鼠灌胃小檗碱150mg/(kg·d),B组大鼠灌胃福辛普利10mg/(kg·d),D组大鼠灌胃小檗碱150mg/(kg·d)+福辛普利10mg/(kg·d),连续给药4周,第8周末测定大鼠空腹血糖、血脂、体重及心脏指数,左心室插管测定左心室最大收缩/舒张速率,放射免疫法测定血浆及心肌血管紧张素Ⅱ(AngⅡ),Western法测定心肌AT_(1R)及AT_(2R)。结果:糖尿病心肌病模型组大鼠空腹血糖、TC、TG、LDL、心脏指数、血浆及心肌AngⅡ、心肌AT_(1R)及AT_(2R)均高于E组大鼠,HDL均低于E组大鼠;与E组相比,心功能出现舒张功能损伤;C组大鼠空腹血糖、TC、TG、LDL、心脏指数、血浆及心肌AngⅡ、心肌AT_(1R)及AT_(2R)显著降低(P<0.01),HDL升高;心脏舒张功能得到改善。结论:小檗碱可以改善糖尿病心肌病大鼠糖、脂代谢紊乱,对其起到一定保护作用。

Objective： To evaluate the potential protective effect and possible mechanism of berberine for rats with STZ-induced diabetic cardiomyopathy.Methods：Male SD rats were randomly divided into group E （control group,n=8）,group A（diabetic model group,n=8）, Berberine group（n=8）, Fosinopril group and Berberine ＋ fosinopril group. Diabetes was induced by a single intraperitoneal injection of STZ（45mg/kg）. Blood glucose 〉16.7 mmol/L 72 h after the injection indicated successful establishment of diabetes. The rats were given 150 mg/（kg.d） berberine, 10 mg/（kg.d） fosinopril and 150 mg/（kg.d） herberine as well as 10 mg/（kg.d） fosinopril for Berberine group, Fosinopril group, and combination group respectively four weeks after the modeling. All intervention lasted for 4 weeks. Blood glucose, blood lipids, body weight and cardiac index were recorded. Besides, ELISA was used to measure myocardial and blood AnglI concentration in the rats,as well as myocardial ATtR and AT2a expression was determined by Western-blot. Results：Fasting blood glucose, TC, TG, LDL, cardiac index, plasma and myocardial Ang Ⅱ, myocardial ATIR and AT2R level of diabetic model group was significantly higher than that of normal control group（P〈0.001）. The absolute values of HDL and -dp/dtmax of diabetic model group were lower than thal of normal control group（P〈0.001）. Fasting blood glucose, TC, TG, LDL, cardiac index, plasma and myocardial Ang Ⅱ, myocardial AT1R and AT2R level of Berberine group was significantly lower than that of the diabetic model group （P〈0.001）, while the absolute values of HDL and -dp/dtmax were significantly higher（P〈 0.001）.Conelusions：Berberine may improve glucose and lipid metabolism disorders in diabetic cardiomyopathy rats, and might have certain protective effect for early diabetic cardiomyopathy rats.