The Research Of Valsartan On Renal Antioxidant In Type2 Diabetic Rats

Objective: Diabetic Nephropathy(DN) is one of the most severe capillary complication of diabetes(DM).And it is the mian reason to cause dead for diabetes patients.There are apparente oxidative stress existing in DN. Oxidative stress means the balance in vivo Between active oxygen and antioxygen defense function is confused. Recently research indicated, AngⅡreceptor antagonist may retrieve derangement of renal hemodynamics in the morning of DM. It may lessen the alteration of nephridial tissue pathology and prevent beforehand interstitial fibrosis. This experiment is to observe the influence of renal lesions and mechanism of action in antioxygen for Angiotensin ReceptorⅠ(Valsartan),to investigate this kind inhibitory action whether or not concerned with down regulation p22phox mRNA expression in diabetes rats .Methods: A rat model of type 2 diabetic nephropathy (DN) was developed successfully by combination of dietary induced insulin resistance and low dose STZ induced hyperglycemia after unilateral nephrectomy. male SD rats were randomly divided into three groups:control rats, type 2 diabetic rats and type 2 diabetic rats treated with Valsartan (10mg/kg/d). After 6 weeks, Content of malonaldehyde (MDA) and activit y of antioxidant enzymes including superoxide dismutase (SOD), in the renal tissue were compared among the groups。In addition, blood glucose, serum creatinine(Scr), urea nitrogen(BUN) and urinary protein were measured respectively. P22phox gene expression was studied with a RT- PCR technique.Results:1)Compare with model group, urinary albumin obviously grow downwards in treatment group( P< 0. 05). The lever of urea nitrogen is breakdown( P<0. 05), The kidney index number of hypertrophia is to improve.2) The content of MDA in kidney obviously descend in treatment group( P< 0. 05). The liveness of liveness of SOD significant upgrade( P < 0. 05).3) The relative amount of p22phox mRNA is 0. 875±0. 94 in the model group, obviously higher than the comparement group(0. 297±0. 067) (P< 0. 01). The relative amount of p22phox mRNA is 0. 484±0. 064 in the treatment group, obviously depressed than the model group( P< 0. 05),But it is also higher than the comparement group( P<0. 05).Conclusion:1)Valsartan can lessen the pathological lesion of nephridial tissue and postpone the process of renal lesions in DM rats.2)Valsartan can inhibit expression of P22phoxmRNA in nephridial tissue and lessen oxidative stress reaction in DN.3) Oxidative stress takes key point in the development of DN, and antioxidation may be the possible mechanism of the neohroprotective action of Valsartan and Valsartan can ameliorate renal lesions in diabetic rats through inhibition of NADPH.