Role of 20-HETE in amelioration of renal impairment by bezafibrate in mice with diabetic nephropathy / 中国药理学通报

ABSTRACT

Aim To investigate the protective effect of bezafibrate on renal injury and the changcs of 20- HETE in mice with diabetic nephropathy. Methods A diabctic model was established by long-term high-energy feeding combined with streptozotocin. The structural and functional changes of kidney were evaluated by renal pathological examination and blood urea nitrogen (BUN), serum creatinine ( Scr) , urinary albumin levels. The expressions of PPAIls and CYP4A protein were detected by Western blot. The level of 20-HETE was measured by ELISA kit. Results After four weeks with high-energy feeding, streptozotocin (40 mg • kg-1 • d"1 i. p) administration had been performed for five days. Then after seven days,fasting blood glucose (FBG) of mice exceeded 11.1 nimol • L"1, which suggested the establishment of the diabetic model. After four weeks of diabetic onset, the levels of BUN,Scr,urinary albumin increased significantly (P er and thickened basement membrane were observed in diabetic mice. Meanwhile,the expressions of PPARs and CYP4A protein in the kidney and the content of 20-HETE in serum decreased in model group (P <0. 01). With bezafibrate supplementation (75 mg • kg"' • d"1) for four weeks, both the structure and function of kidney were improved in diabetic mice,with the up-regulation of PPARs and CYP4A protein expressions and the increase of 20-HETE level (P <0. 01 ). Conclusions Bezafibrate can ameliorate renal injury in diabetic mice, which may be related to activating CYP4A-20-HETE.