大黄酸和苯那普利联合治疗db/db糖尿病小鼠的疗效观察  

Combined therapy of rhein and benazepril for treatment of diabetic nephropathy in db/db mice

作　　者：贾忠辉[1] 刘志红[2] 郑敬民[2] 曾彩虹[2] 黎磊石[2] 

机构地区：[1]南京大学医学院临床学院 [2]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《肾脏病与透析肾移植杂志》2006年第2期112-119,共8页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的:观察大黄酸和苯那普利对糖尿病db/db小鼠肾脏损伤的保护作用,比较二者疗效的差别,同时探讨大黄酸联合苯那普利治疗2型糖尿病肾病的疗效。方法:8周龄的db/db和db/m小鼠分为五组:A:db/m正常小鼠对照组;B:db/db糖尿病小鼠对照组;C:db/db糖尿病小鼠大黄酸[150mg/(kg·d)]治疗组;D:db/db糖尿病小鼠苯那普利[10mg/(kg·d)]治疗组;E:大黄酸[150mg/(kg·d)]联合苯那普利[10mg/(kg·d)]治疗组。于不同治疗时间(4周、8周、12周)测定各组体重、血糖、血脂(胆固醇、三酰甘油、高密度脂蛋白、低密度脂蛋白)、血肌酐、24h尿白蛋白水平。肾组织病理切片行HE、PAS染色,采用图像分析软件对肾小球病理形态学改变进行定量分析。免疫病理观察肾组织转化生长因子(transforminggrowthfactor-β,TGF-β)以及纤维粘连蛋白(fibronectin,FN)的表达,并行半定量评分。结果:大黄酸组在治疗8周时体重、血糖、胆固醇、低密度脂蛋白、24h尿白蛋白排泄较糖尿病对照组均有明显下降(P<0·05),治疗12周时肾小球肥大、基质增生较糖尿病对照组明显改善,TGF-β、FN在肾小球中表达下调;苯那普利组治疗8周时24h尿白蛋白排泄较糖尿病对照组明显下降(P<0·05),治疗12周同样可减轻肾组织病变;大黄酸联合苯那普利组治疗第4周就能明显降低胆固醇、减轻尿白蛋白排泄,并且在治疗12周时血肌酐水平较糖尿病对照组明显下降(P<0·05),肾小球肥大以及基质增生较糖尿病对照组改善更为明显,同时TGF-β以及FN的表达下调更为显著。结论:大黄酸可改善db/db小鼠的肥胖程度、降低血糖、脂代谢紊乱,同时能降低尿白蛋白的排泄、改善肾功能,明显减轻db/db小鼠的肾脏病变;苯那普利同样可降低尿白蛋白排泄,改善肾功能,减轻肾组织病理改变。大黄酸和苯那普利联合治疗较单独用药更早的降低尿白蛋白排泄和改善血脂水平,同时改善肾功能Objective： In this study, we compared effects of rhein and angiotensin-converting enzyme inhibitor （ACEI） on renal injury in non-insulin dependant diabetes mellitus, and evaluated the combined effects of rhein and ACEI in diabetic nephropathy in db/db mice. Methodology ： db/db and db/m mice of 8 weeks of age were divided into five groups according to the treatment： group A （db/m mice with saline treatment）, group B （db/db mice with saline treatment）, group C [ db/db mice with rhein treatment at dosage of 150mg/（ kg· d） ], group D [ db/db mice with benazepril treatment at dosage of 10 mg/（kg·d） ], and group E [ db/db mice with combined treatment of rhein at dosage of 50 mg/kg·d and benazepril at dosage of 10 mg/（kg·d） ]. Body weight , blood glucose, lipids level,24h urinary albumin excretion were measured every 4 weeks. Morphometry of renal tissue and immunostaining of transforming growth factor-β1 （ TGF-β1 ） and fibronectin were performed in all groups at the end of the study. Results： Body weight, blood glucose, cholesterol, triglycide and low density lipoprotein were all decreased in the group C and the group E than in group B after treatment（ P 〈 0. 05 ）. Urinary albumin excretion were reduced after 4 weeks treatment in group E, and after 8 weeks treatment of in group C and group D groups as compared to the control of group B （ P 〈 0. 05 ）. Plasma creatinine level decreased significantly as compared with diabetic control of group E at the end of experiment. Histological morphometric analysis revealed that the whole glomerular area （WGA） and extracellular matrix area （ECMA） were significantly reduced in group C, group D and group E as compared to group B at the 20th week of age, with the most decrement observed in group E. In immunohistochemistry study, both glomerular and tubulointerstitial TGF-β1 expression decreased in groups C, group D and group E as compared to that in group B at the 20th week of age. Conelusion：A similar renal protective eff

关 键 词：大黄酸 苯那普利 DB/DB小鼠 糖尿病肾病 

分 类 号：R587.1[医药卫生—内分泌] R544.105[医药卫生—内科学]