Effects Of PPARγ Agonist On Serum Adiponectin,Urine Microalbumin And Renal Pathology Of Obese Mices

Objective:Obesity has become a worldwide epidemic, the incidence of obesity is an increasing trend. Obesity and metabolic syndrome cause complex metabolic disorders due to insulin resistance and chronic inflammation,leading to diabetes mellitus, hypertension, hyperlipidemia, atherosclerosis, coronary heart disease and damage of other organs including kidney. This study took pathogenesis of obesity-related glomerulopathy(ORG) and action mechanism of peroxisome proliferator-activated receptor y(PPARγ) agonist as the theoretical basis,evaluated the effects of PPARγ agonist on serum adiponectin(ADP), urine microalbumin(mALB) and kidney pathology of obese mices and explored the significance of PPARy agonists preventing ORG.Methods:16male OB mices and8male C57mices which were8weeks old in this study. Dividing OB mices into2groups randomly according to body mass:obesity group(M group) and Pioglitazone intervention group(T group) which were fed with high lipid chow.C57mices were control group(C group) which were fed with ordinary chow. Mices in T group were administered with Pioglitazone(12.5mg·kg-1·d-1) by gavage daily. Mices in M group and C group were administered with distilled water equal gavage daily for12weeks.Body mass,blood glucose,serum ADP,urine mALB were assayed in each group and compared.After12weeks, the mices were sacrificed, and the kidneys of mices were obtained and weighed.Observe the morphological changes of kidneys by HE staining, measure and compare glomerular diameters.Positioning zonula occludens-1(ZO-1) and Wilms tumor1(WT1) by immunohistochemistry, evaluate and compare the level of expression of ZO-1in podocyte and podocyte number which was signed with WT1in each group.And then study the correlations between serum ADP,urine mALB and body mass.blood glucose, kidney mass,glomerular diameter,the level of expression of ZO-1, podocyte number.The statistical analysis of the data was done with the statistical package of SPSS17.0. A value of P<0.05was considered statistically significant. Results:1.The body mass in M group and T group were more than20%of that in C group,that accorded with the standard of obese mice.The blood glucose in each group was less than16.7mmol/L,that excluded diabetes mellitus of mice.2. At the beginning of the experiment,the serum ADP in each group were similar, and there was no significant difference(P>0.05);the urine mALB in M group and T group were more than that in C group, and the difference was statistically significant (P<0.05). By the end of the experiment, the serum ADP in T group was significantly highter than that in C group and M group(P<0.05, P<0.01);the urine mALB in M group was more than that in C group, and the difference was statistically significant(P<0.05), the urine mALB in T group was less than that in M group, and the difference was statistically significant(P<0.01),but no statistical difference with C group(P>0.05).In addition, the serum ADP after the experiment was lower than that before the experiment in M group,and the difference was statistically significant (P<0.05);the urine mALB after the experiment was lower than that before the experiment in T group,and the difference was statistically significant(P<0.01).3.The kidney mass in M group was more than that in C group, the kidney mass in T group was more than that in C group and less than that in M group,and the difference was statistically significant(P<0.01).Glomerular volume increased significantly and in part associated with focal segmental glomerulosclerosis in M group,but there were no glomerular hypertrophy and glomerulosclerosis in T group. The glomerular diameter in M group was significantly bigger than that in C group(P<0.05).The glomerular diameter in T group was significantly smaller than that in M group(P<0.01), but no statistical difference with C group(P>0.05). The level of expression of ZO-1and podocyte number in M group were significantly lower than that in C group(P<0.05, P<0.01).The level of expression of ZO-1and podocyte number in T group were significantly highter than that in M group(P<0.05), but no statistical difference with C group(P>0.05).4.The results of linear correlation analysis revealed that the serum ADP was in negative correlations with urine mALB(r=-0.538,P<0.01),glomerular diameter (r=-0.411,.P<0.05),and in positive correlations with level of expression of ZO-1 (r=0.421,P<0.05),podocyte number(r=0.409,P<0.05),but had no significant correlations with body mass,blood glucose and kidney mass(P>0.05).The urine mALB was in positive correlations with kidney mass(r=0.457,P<0.05),glomerular diameter(r=0.529,P<0.01),and in negative correlations with serum ADP(r=-0.538, P<0.01),level of expression of ZO-1(r=-0.437,P<0.05),but had no significant correlations with body mass,blood glucose and podocyte number(.P>0.05).Conelus ions:1.The animal model used in this study was spontaneous mutation OB mice whose blood glucose was highter than normal but below the diagnostic criteria for diabetes mellitus, so it was ideal animal model for the study of human obesity.2.The serum ADP of obese mice decreased,the urine mALB of them increased,and there was a negative correlation between serum ADP and urine mALB.Renal pathology showed glomerular hypertrophy, in part associated with focal segmental glomerulosclerosis,the expression of ZO-1in podocyte and podocyte number reduced.The kidneys of obese mice had clinical and pathological changes indicating that obesity can lead to kidney damage.3.Pioglitazone can make the low serum ADP level of obese mice ameliorated,and make the urine mALB of them reduced.Renal pathological change significantly alleviated, the expression of ZO-1in podocyte and podocyte number were increased, indicating pioglitazone can improve renal injury related to obesity.The results reveal that PPARγ agonists may provide a new avenue of prevention and treatment of ORG.