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  

Comparison of therapeutic effects of ethanol extracts of compound 4 Rehmannia decoction with aminoguanidine on diabetic and cardiomyopathy in streptozotocin induced diabetic rats

作　　者：张媛[1] 纳涛[2] 戴德哉[2] 袁盛华[2] 刘浩然[2] 戴茵[2] 

机构地区：[1]中国食品药品检定研究院,北京100050 [2]中国药科大学药理研究室,南京200019

出　　处：《药物分析杂志》2011年第11期2046-2053,共8页Chinese Journal of Pharmaceutical Analysis

摘　　要：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 streptozotoein（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; hemodynamies 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.

关 键 词：中药 四味地黄 地黄 氨基胍(AMG) 纤维化 内皮 糖尿病 心肌病 一氧化氮(NO) 

分 类 号：R917[医药卫生—药物分析学]