四味地黄乙醇提取物治疗糖尿病心肌病与氨基胍药效比较

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 effectiveness of 95% and 70% ethanol extracts (EtOH Ext) of compound Rehmannia decoctions in treating diabetic cardiovascular complications and compare the effect with aminoguanidine(AMG) in streptozotocin(STZ) induced diabetic rats. Methods: Diabetic were induced in rats by STZ(60 mg·kg^-1,intraperitoneal injection,i.p.) with development period of 8 weeks.The diabetic rats were treated with AMG (100 mg·kg^-1,intragastric administration,i.g.),70% EtOH Ext(10 g·kg^-1,i.g.) and 95% EtOH Ext (10 g·kg^-1,i.g.) respectively from 5th week to 8th week after STZ treated.Endothelium-dependent relaxation of mesentery artery rings;blood glucose and cholesterol(CHO) in serum;catalase(CAT),nitric oxide(NO),nitric oxide synthases(NOS),hydroxyproline(HYP) in the myocardium;hemodynamics and heart weight index were conducted. Results: After 8 weeks of STZ inducement,the endothelium-dependent relaxation/contraction of mesentery artery rings was impaired.Glucose and CHO level in serum were increased(P<0.01).Inducible nitric oxide synthase(iNOS),total nitric oxide synthase(tNOS) and HYP in the myocardium were remarkedly elevated by +59.7%,+50.0% and +26.6%(P<0.01,P<0.01, P<0.01),and CAT activity was decreased by -14.6%(P<0.05).All these abnormalities in diabetic rats were relieved by AMG and/or the two EtOH Ext of Rehmannia decoctions. Conclusions: Vascular abnormality and cardiomyopathy in STZ induced diabetic rats were linked with advanced glycation end-products(AGEs) which can be suppressed by selective blocker AMG,and the EtOH Ext of Rehmannia decoction.