Effects of aminoguanidine and vitamin C on collagen type IV in diabetic nephropathy rats

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ORIGINAL ARTICLE

Effects of aminoguanidine and vitamin C on collagen type IV in diabetic nephropathy rats Qiangxiang Li • Xiang Ao • Youhong Du • Yang Li • Yangshi Ou • Raofeng Gong • Xuexiong Sun • Yi Xiang Yang • Gebo Wen

Received: 17 June 2010 / Accepted: 25 October 2010 / Published online: 18 November 2010 Ó Springer Science+Business Media, LLC 2010

Abstract The aim of this article is to investigate the effects of Aminoguanidine and vitamin C (VitC) on type IV collagen in diabetic nephropathy rats. Diabetic nephropathy rats were induced by intraperitoneal injection of STZ. Rats were randomly divided into five groups: normal control group (n = 10), diabetes group (n = 10), aminoguanidine group (n = 10), VitC group (n = 10), aminoguanidine and VitC group (n = 10). After 16 weeks, the general conditions, blood gloucose, glycosylated hemoglobin, blood urea nitrogen, serum creatinine, serum type IV collagen, urinary albumin excretion rate, and creatinine clearance rate were detected, type IV collagen protein was determined by immunohistochemical analysis as well as the expression of collagen type IVa1 mRNA were determined by in situ hybridization analysis in the

kidneys of each group. The results were (1) diabetes mellitus and renal lesions occurred in the diabetes group, aminoguanidine group, VitC group, VitC and aminoguanidine group; (2) aminoguanidine and VitC improved the general conditions of diabetic nephropathy rats, decreased blood urea nitrogen, serum creatinine, and urinary albumin excretion rate as well as increased creatinine clearance rate. The expressions of collagen type IV were significantly down-regulated in treatment groups in contrast to the diabetes group. Aminoguanidine and VitC protect renal lesions in diabetic nephropathy, respectively, by inhibiting expression of type IV collagen, while aminoguanidine and VitC have a synergistic effect on them. Keywords Aminoguanidine  Vitamin C  Diabetic nephropathy  Type IV collagen

Qiangxiang Li and Xiang Ao contributed equally to this work.

Introduction Q. Li  G. Wen (&) Clinical Research Institute, The First Affilliated Hospital, NanHua University, Henyang, Hunan 421001, China e-mail: [email protected] X. Ao Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China Q. Li  Y. Du  R. Gong  X. Sun  Y. X. Yang Loudi Municipal Central Hospital of Hunan, Loudi 417000, China Y. Li Maternal and Child Health Hospital of Hunan Province, Changsha 410008, China Y. Ou Liberation Army 458 hospital of Guangdong province, Guangzhou 510602, China

Diabetic nephropathy is characterized by glomerular extracellular matrix (ECM) accumulation, glomerulosclerosis, and progressive tubulointerstitial fibrosis, yet the pathogenesis is not completely clear. Early diagnosis and treatment are very important. Type IV collagen accounts for 50% of dry weight of glomerular basement membrane (GBM) in the normal mesangial matrix. It is one of the important components of glomerular capillary basement membrane and a marker of the mesangium, reflecting th