The Effect Of Telmisartan On The Expression Of Pparγ And Nnos In Rats With 5/6 Nephrectormy

Objective: To observe the expression of renal peroxisome proliferator activated receptor gamma(PPARγ)and neuronal nitric oxide synthase(nNOS)in rats with 5/6 nephrectomy, and the effect of angiotensinⅡAT1 receptor antagonist telmisartan for the expression of both. To explore the role of telmisartan on the activation of PPARγin renal tissue rats with 5/6 nephrectomy and the possible mechanisms of renal protection.Methods: 180-200gSD rats with 5/6 nephrectomy were randomly divided into sham-operation group, model group, telmisartan group, telmisartan + GW9662 group and rosiglitazone group. At the end of 12th week, blood and urine samples in each group were taken to detect the level of the serum urea nitrogen, creatinine and 24h urinary protein. Then rats were killed with decapitation method, and residual kidney tissue were obtained for pathological examination to determine glomerular sclerosis and tubulointerstitial injury. The distribution of PPARγand nNOS in the kidney tissue of the 5 groups were detected by using immunohistochemistry. The expression of PPARγand nNOS for mRNA and protein level were detected by RT-PCR and Western Blot respectively, and the correlation between PPARγand nNOS was analyzed.Results: Compared with the sham group, for example, the levels of blood urea nitrogen, creatinine and 24h urine protein in model group, telmisartan group, telmisartan + GW9662 group and the rosiglitazone group were all abnormally increased (P<0.01); Compared with model group, however, the level of these parameters in telmisartan group, telmisartan + GW9662 group and the rosiglitazone group were much lower (P<0.05); The parameters in telmisartan group were much better than in telmisartan + GW9662 group (P<0.05). Model group had obvious renal glomerular sclerosis and tubulointerstitial damage. Compared with the sham group, the index of glomerular sclerosis and tubulointerstitial damage in model group were significantly worse (P<0.01); but telmisartan group had a comparative better result compared with model group and telmisartan + GW9662 group (P<0.05). The immunohistochemistry results showed that PPARγmainly distributed in the areas of renal tubular epithelial cells, mesangial cells and infiltrating macrophages in rats with 5/6 nephrectomy. nNOS in renal cortex was mainly localized in dense patches, inner medullary collecting duct is also expressed. In the terms of the level of gene expression in the 5/6 nephrectomized rats kidney tissue, the expression of PPARγand nNOS for mRNA and protein were decreased in the 5 groups except for the sham group, and they were higherly expressed in telmisartan group than in the telmisartan + GW9662 group (P<0.05), while the relationship of nNOS and PPARγprotein expression in renal tissue telmisartan group and telmisartan + GW9662 group were in positive linear correlation (r = 0.865, P<0.05).Conclusion: SD rats with 5/6 nephrectomy granted with telmisartan, can reduce glomerulosclerosis and renal interstitial fibrosis, thereby reducing the progress of chronic kidney disease. The mechanism may be related to upregulation of PPARγ, thus an increase in nNOS expression. This effect of Telmisartan may be independent of its angiotensin AT1 receptor antagonist effection.