| Objective:Obesity has become the one of the three major diseases (smoking, obesity and HIV/AIDS) which affecting human health.As the obese increased rapidly, it has become an important public health problem.This study took action mechanism of peroxisome proliferator-activated receptor y(PPARy) agonist to non-diabetic obesity-related glomerulopathy(ORG) as the theoretical basis,evaluated the effects of different dosages of PPARy agonist on serum adiponectin(ADP), urine microalbumin(mALB) and kidney pathology of obese mices and explored the significance of PPARy agonists preventing ORG.Methods:32male OB mices and8male C57mices which were8weeks old in this study. Dividing OB mices into4groups randomly according to body mass:obesity group(M group) and low dosage pioglitazone intervention group(Tl group),medium dosage pioglitazone intervention group(T2group),high dosage pioglitazone intervention group(T3group)which were fed with high lipid chow.C57mices were control group(C group) which were fed with ordinary chow. Mices in T1group were administered with Pioglitazone(12.5mg·kg-1·d-1) by gavage daily,T2group (25mg-kg-1-d-1),T3group (50mg-kg-1-d-1).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 T1,T2,T3groups 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 T1,T2,T3groups and M 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 T1,T2,T3groups were significantly highter than that in C group and M group(P<0.05, P<0.01), and T2,T3groups were highter than that in T1group,but there was no statistical difference between T2group and T3group(P>0.05); the serum ADP after the experiment was lower than that before the experiment in M group, and the serum ADP after the experiment was highter than that before the experiment in T1,T2,T3groups,and the difference was statistically significant (P<0.05), there was no statistical difference between before and after the experiment in C group(P>0.05),the urine mALB in M group and T1,T2,T3groups were more than that in C group, and the difference was statistically significant(P<0.05), By the end of the experiment, the urine mALB in M group was highter than that in C group(P<0.05),Tl,T2,T3groups were significantly lower than that in M group(P<0.05, P<0.01), and T2,T3groups were lower than that in T1group,but there was no statistical difference between T2group and T3group(P>0.05); In addition,the urine mALB after the experiment was lower than that before the experiment in T1,T2,T3groups,highter than that in C group and M group (P<0.01).3.The kidney mass in M group was more than that in C group, the kidney mass in T1,T2,T3groups were 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 T1,T2,T3groups. The glomerular diameter in M group was significantly bigger than that in C group(P<0.05).The glomerular diameter in T1group was significantly smaller than that in M group(P<0.01), but no statistical difference with C group(P>0.05). The glomerular diameter in T2,T3groups were significantly smaller than that in T1,C groups(P<0.05), there was no statistical difference between T2group and T3group(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 T1, T2, T3groups were significantly highter than that in M group(P<0.05), but no statistical difference with C group(P>0.05).T2has no difference with T3group.4.The results of linear correlation analysis revealed that the serum ADP was in negative correlations with urine mALB(P<0.01),glomerular diameter (P<0.05),and in positive correlations with level of expression of ZO-1(P<0.05),podocyte number (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(P<0.05),glomerular diameter(P<0.01),and in negative correlations with serum ADP(P<0.01),level of expression of ZO-1and podocyte number (P<0.05),but had no significant correlations with body mass,blood glucose (P>0.05).Conclusions: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 non-diabetic obesity.2. Different doses of 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 different doses of pioglitazone can improve renal injury related to obesity.3.The dose of peroxisome proliferator-activated receptor y(PPARy) agonist is closely related to the serological and urine marker and the improvement degree of renal pathology in non-diabete obesity mice. High dose of peroxisome proliferator-activated receptor y agonist is more advantageous to the prevention and control of obesity-related glomerulopathy in non-diabetic and obesity mice. |
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