Protective Effect Of Valsartan On The Podocytes Of Diabetic Rats

Objective To observe the effects of valsartan on the podocin expression in podocytes of diabetic rats and to explore the mechanism of valsartan (an angiotensin Ⅱ receptor antagonist) on the kidney of diabetic rats.Methods Thirty-six healthy Sprague-Dawley rats were randomly divided into two groups(normal control group and experimental group). Rats in experimental group were given streptozocin(STZ) by intrapetitoneal injection to establish animal models of diabetes, then the rat models were randomly divided into DN group and valsartan-treated group.Furthermore,After 8 weeks, glycated hemoglobin (HbA1C),urinary albumin (UALB), urinary creatinine (UCR), urinary retinol binding protein (URBP) and Kidney hypertrophy index(KI) were determined, to eliminate the impact of urine volume, the parameters mentioned above were expressed as UALB /UCR(UACR),URBP/UCR(UBCR). Blood glucose was measured weekly in all groups. The expression of podocin protein and mRNA in renal tissues were detected by immunohistochemistry and RT-PCR method. The renal histomorphology and the structural change of podocytes was observed through optic microscope and electron microscope.Results1.8 weeks later,Compared to normal control group, BG, UACR, UBCR, HbA1C, KI were markedly higher in normal control group and valsartan-treated group (P<0.01). Compared to DN group, except for BG and HbA1C, the obove indexes were significantly decreased in valsartan-treated group (P<0.01),2.8 weeks later, Immunohistochemical results show that podocin is linear distribution along the glomerular capillary loops and strong positive expression in normal control group. In group DN, the expression of podocin protein was significantly weakened or reduced. Compare to group DN,it was increased in valsartan-treated group. The podocin protein expression in group valsartan-treated group was significantly higher than that in normal control group (P<0.01).3.8 weeks later, Under the high power lens, it was observed that the glomerular volume were hypertrophied and mesangial matrix increased and extracelluar matric proliferated in group DN by HE staining.Compare to group DN,the above pathological changes were significantly improved in normal control group.4.8 weeks later, in normal control group,the results showed the podocytes structure was normal, and the glomerular basement membrane uniform by electron microscopes. In group DN, the foot processes were markedly destroyed and GBM was much thicker, even vanished.Compared with normal control group, the difference was significant (P<0.01). In valsartan-treated group, a small amount of podocyte foot process fusion,GBM without obvious thickening.Compared with the DN group, there were statistically differences(P<0.01).5. Via semiquantitative RT-PCR detection, podocin mRNA expression of kidney of normal control group was higher than it in group DN and normal control group.Compared to DN group, the expression of podocin mRNA showed a better improvement in valsartan-treated group(P<0.01).Conclusion Valsartan exert the protective effect on the podocytes in diabetic rats, the mechanism may be achieved by the up-regulatied expression of Podocin protein and mRNA,and prevent the loss of urinary protein to relieve the kidney disease.