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目的:研究四味地黄2种醇提取物对STZ诱导糖尿病大鼠心肌病及血管病变的药效,与AGEs选择性阻断剂氨基胍比较。方法:腹腔一次注射60 mg.kg-1链脲佐菌素(STZ)建立糖尿病大鼠模型,4周后随机分组,5～8周分别灌胃:100 mg.kg-1氨基胍(AMG),10 g.kg-1复方地黄70%乙醇提取物,或10 g.kg-1 95%乙醇提取物。8周后,测定肠系膜动脉内皮依赖性舒张、血流动力学及心脏重量指数,血清中血糖、胆固醇(CHO),心肌组织中过氧化氢酶(CAT)、一氧化氮(NO)、一氧化氮合酶(NOS)、羟脯氨酸(HYP)。结果:STZ诱导的糖尿病大鼠血管内皮功能受损,血管内皮依赖性舒张减弱;血流动力学参数反映心功能明显下降,心肌肥大。血清中血糖与CHO含量较正常组显著升高。心肌组织中iNOS及tNOS分别较正常组大鼠升高+59.7%及+50.0%(P<0.01,P<0.01),CAT(U.mg prot-1)而活性降低-14.6%(P<0.05),HYP(μg.mg prot-1)含量显著增高+26.6%(P<0.01)。氨基胍和2种乙醇提取物,均明显改善糖尿病的血管与心脏的并发症,但无明显的降糖作用。95%乙醇提取物的疗效,对一些指标好于70%乙醇提取物。结论:四味地黄制剂的2种乙醇提取物均能明显改善糖尿病心肌病和血管病变、疗效与氨基胍基本一致。疗效可能与阻断AGEs有关。95%醇提取物的酯溶性组分对消除心肌纤维化药效更重要。
OBJECTIVE: To study the pharmacodynamic effects of two alcoholic extracts of four flavonoids on cardiomyopathy and vasculopathy in STZ-induced diabetic rats, compared with aminoguanidine, a selective antagonist of AGEs. Methods: A diabetic rat model was established by intraperitoneal injection of 60 mg · kg -1 streptozotocin (STZ). After 4 weeks, the rats were randomly divided into groups and were administered with 100 mg · kg -1 aminoguanidine (AMG) , 10 g.kg-1 Compound Rehmannia 70% ethanol extract, or 10 g.kg-1 95% ethanol extract. After 8 weeks, the endothelium-dependent relaxation of mesenteric artery, hemodynamics and heart weight index, serum glucose, cholesterol (CHO), catalase (CAT), nitric oxide (NO) Nitrogen synthase (NOS), hydroxyproline (HYP). Results: The vascular endothelial function of STZ-induced diabetic rats was impaired, and the endothelium-dependent relaxation of blood vessels was weakened. The hemodynamic parameters showed that cardiac function was significantly decreased and cardiac hypertrophy. Serum glucose and CHO levels were significantly higher than the normal group. The activity of iNOS and tNOS in myocardium were increased by 59.7% and + 50.0% (P <0.01, P <0.01) and CAT (U.mg prot-1) ), HYP (μg.mg prot-1) was significantly increased + 26.6% (P <0.01). Aminoguanidine and two kinds of ethanol extract, both significantly improve the vascular complications of diabetes and heart, but no significant hypoglycemic effect. Efficacy of 95% ethanol extract, for some indicators better than 70% ethanol extract. Conclusion: The two kinds of ethanol extract of four-flavoring preparation can significantly improve diabetic cardiomyopathy and vascular disease, and the curative effect is basically consistent with that of aminoguanidine. Efficacy may be related to blocking AGEs. The 95% alcohol extract of the ester-soluble components of the elimination of myocardial fibrosis efficacy is more important.