Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats  

作　　者：Ravi Prakash Rao Ansima Singh Arun K Jain Bhartu Parsharthi Srinivasan 

机构地区：[1]Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), New Delhi 110017, India [2]Department of Pharmaceutical Science, Birla Institute of Technology, Mesra, Ranchi 201301, India [3]Institute of Pathology, Indian Council of Medical Research (ICMR), New Delhi 110029, India

出　　处：《The Journal of Biomedical Research》2011年第6期411-417,共7页生物医学研究杂志（英文版）

摘　　要：Diabetic nephropathy is a major cause of end-stage renal disease （ESRD） in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin （90 mg/kg） in neonatal rats and then these rats were treated with rosiglitazone （1.0 mg/kg） in combination with glimepiride （0.5 mg/kg） or with pioglitazone （2.5 mg/kg） in combination with glimepiride （0.5 mg/kg）. Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.Diabetic nephropathy is a major cause of end-stage renal disease （ESRD） in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin （90 mg/kg） in neonatal rats and then these rats were treated with rosiglitazone （1.0 mg/kg） in combination with glimepiride （0.5 mg/kg） or with pioglitazone （2.5 mg/kg） in combination with glimepiride （0.5 mg/kg）. Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.

关 键 词：type 2 diabetes mellitus diabetic nephropathy peroxisome proliferator activated receptors （PPARs） transforming growth factor-β1 （TGF-β1） tumor necrosis factor-α （TNF-α） 

分 类 号：R587.1[医药卫生—内分泌]