Renoprotection of diabetic rats with losartan

Objective:To study the renoprotective effect and mechanism of angiotensin Ⅱreceptor blocker(ARB)-losartan in diabetic rats.Methods: Thirty-six rats were randomly assigned into three groups: healthy control(n=12),diabetic control(n=12),or losartan administration(n=12).The diabetic model of rats were set up by subabdominal injection with strephtozotocin 65 mg·kg-1.After one week post the diabetic model,the rats were fed with losartan 5 mg·kg-1·d-1 for 12 weeks.Levels of blood glucose and excretion rates of urinary albumin and retinal-bindiog protein(RBP) were analyzed at the end of the 1 st-,4 th-and 12 th-week administration of losartan.The rats were sacrificed to collect renal tissues for the measurement of renal hyperplasia index by weighing and the expressions of TGFβ1 mRNA in the renal cortex by a fluorescent RT-PCT assay at the end of the 4 th-and 12 th week administration of losartan.The histopathological examinations on the glomerular basement membrane and the mesangium of diabetic rats were conducted by electron microscopy at the end of the 4 th-and 12 th-week administration of losartan.Results: Compared with the healthy control rats,the excretion rates of urinary albumin and RBP,the renal hyperplasia index and expression of TGFβ1 mRNA were significantly escalated in diabetic rats at the end of the 4 th and 12 th week(P0.01).The losartan-treated rats showed significant improvements of those episodic focal signs and indexes compared with the diabetic rats(P0.01).The electron microscopy showed that the losartan-treated rats had less hyperplasia of glomerular basement membrane and mesangium than the diabetic rats.Conclusion: Losartan prevented rats from diabetic nephropahty by down-regulating TGFβ1 mRNA expression in renal tissue.