Renoprotective effect and mechanism of pioglitazone in KKAy mice

Abstract

Objective To investigate the effect of pioglitazone on serum adiponectin (ADP), urinary albumin creatinine ratio (UACR) and renal pathology of KKAy mice, and discuss the mechanism of pioglitazone preventing and treating diabetic nephropathy(DN). Methods Sixteen male KKAy mice (12 weeks old) were randomly divided into 2 groups according to blood glucose: diabetes mellitus group (D group) and pioglitazone treatment group (P group), which were fed with high lipid chow. Meanwhile, eight male C57BL/6 mice as the control group (C group) which were fed with ordinary chow for 12 weeks. Serum ADP, UACR were assayed in each group. Renal pathology was observed by light microscope and electron microscope. Wilms tumor 1, zonula occludens-1 (ZO-1), AMP activated protein kinase (AMPK) and NADPH oxidase-4 (NOX-4) were positioned and evaluated by immunohistochemistry in each group. The data of three groups were analyzed by single factor analysis of variance, and the data of two groups were compared with independent samples t test. Results The level of UACR in P group ((75±9) μg /mg) was lower than that before therapy ((121±19) μg /mg) and that in D group((159±20) μg /mg, t=3.864, 4.975, both P<0.01). The serum ADP in P group ((67±6) μg/ml) was higher than that in D group((39±14) μg/ml, t=4.087, P<0.01). Renal pathology was significantly alleviated. The podocyte number, ZO-1 and AMPK in P group were higher than that of D group(t=2.036, 2.585, 2.947, all P<0.05). NOX-4 in P group was lower than that of D group(t= 3.612, P<0.01). Conclusions One of the possible mechanism of pioglitazone preventing and treating DN may be to increase the level of ADP, up-regulate AMPK, inhibit NOX-4, relieve oxidative stress and repair injured podocyte. Key words: Diabetic nephropathies; Oxidative stress; Adiponectin; Mice; Pioglitazone