Protective Effect Of Enalapril And Weight Reduction On Podocyte Lesion Of Obesity Related Glomerulopathy Rats

1.The establishment and evaluation of rats model of obesity related glomerulopathy Objective To establish and evaluate a new rat model of obesity related glomerulopathy (ORG).Methods Seventy-two male Wistar rats were randomly divided into two groups:normal control group((NC,n=12)),model group(ORG,n=60).NC rats and ORG rats respectively were fed by underlaying forage fed and by high lipid forage for 24 weeks,Body weight(BW), Lee's index number,mean arterial pressure(MAP),fasting plasma glucose(FBG),total cholesterol(TC),triglyeride(TG),free fatty acids(FFA),24 hour urine albumen(24hUALb), fasting insulin(FINS) and leptin(LEP) of rats were measured.The renal pathological alterations were observed at 24 week by optics microscope and electronic microscope.Results At the end of 24 weeks,Compared with NC group,BW,Lee's index number, MAP,24hUALb,serum levels of FINS and LEP increased significanty(P＜0.01),serum levels of TG and FFA were higher in model group(P＜0.05).TC had no significant difference between 2 groups(P＞0.05);FBG in 2 groups was within normal limits,but higher in ORG group than in NC group(P＜0.05).Renal pathology in ORG group had a more tremendous alteration than those of NC group,glomerular capsular space was even megaly(P＜0.01), glomerular basement membrane was a little thicker(P＜0.01).Conclusion The results suggest that the high lipid forage feeding could successfully establish the rat model of ORG for clinical practice.2.Protective effect of Enalapril and Weight reduction on podoeyte lesions of obesity related glomerulopathy rats(ORG)Objective To investigate the expression of the WT1 in podocyte of obesity related glomerulopathy(ORG) rat and the mechznism of enalapril and weight reduction-induced renal protection..Methods The ORG model was established by high lipid forage for 24 weeks,and forty male Wistar rats were divided into five groups:normal control rats(group A),ORG rats(group B),enalapril-treated ORG rats(group C),ORG rats with weight reduction(group D) and enalapril-treated ORG rats with weight reduction(group E).At 8 weeks,Body weight(BW), mean arterial pressure(MAP),24 urine albumen(24hUAlb),blood urea nitrogen(BUN) and serum creatinine(SCr) were assayed,and the pathological changes of kidney were detected by optics microscopy and transmission electronic microscopy.Immunohistochemistry was used to detect the expression of WT1,a marker ofpodocyte injury.Results In ORG rats,potocyte number and density were declined remarkably compared with group A(respectively,P＜0.01),and there were significantly higher 24UAlb and obvious kidney damage than these of group A(respectively,P＜0.01).After treatment,potocyte number and density in group(C D E) were significantly increase compared with group (respectively,P＜0.05,P＜0.01).Meanwhile,enalapril and weight reduction reduced 24hUA1b and alleviated kidney damage(respectively,P＜0.01).Still,therapeutic alliance effect in group E outweighed group(C,D).Conclusion Decreased podocyte density and number were observed in ORG,and changes in podocytes correlated with degree of proteinuria and renal function impairment. Enalapril and weight reduction can restrain the expression of WT1 in ORG,which can reduce proteinuria and lessen kidney damage.