The effect of Losartan on the diabetic glomerulus and the level of glomerular cyclin-kinase inhibitor P27

Objective To investigate the relationship between the cyclin kinase inhibitor P27 and the protecting effect of Losartan on the diabetic glomerulus. Methods STZ induced diabetic rats were given Losartan (1 mg·kg -1 ·d -1 or 2 mg·kg -1 ·d -1 )for 8 weeks.The P27 protein of glomerular lysate was detected with western blot analysis. The extracellular matrix (ECM) protein (type Ⅳ collagen and fibronectin) of glomerular lysate and 24 h urine albumin were examined with ELISA. Image analysis system was used to detect area of glomerulus. Results Glomerular area and ratio of kidney weight to body weight elevated in diabetic rats. Meanwhile, the 24 h urine albumin excretion, glomerular ECM and glomerular P27 protein increased in diabetic rats. Losartan decreased glomerular area, the ratio of kidney weight to body weight, 24 h urine albumin excretion as well as glomerular P27 level in diabetic rats. The above effect of Losartan increased as the dose of Losartan increased. The blood glucose remained constant in diabetic rats and Losartan treated diabetic rats. Conclusion Losartan can ameliorate diabetic glomerular hypertrophy through decrement of glomerular P27 level.