Preliminary Study On Hypogonadal Function And Expression And Regulation Of FABP4 In Gonad Of Male Diabetic Nephropathy Rats

Objective:The purpose of this study was to investigate the cellular morphological changes and the expression of Adipocyte Fatty acid-binding Protein 4（FABP4）and Forkhead box o1（FOXO1）in the testis of type 2 diabetes Mellitus（T2DM）and diabetic nephropathy rats,and to detect the levels of serum Testosterone（T）,Follicular stimulating hormone（FSH）and Luteinizing hormone（LH）,to investigate the etiology and mechanism of Type 2 diabetes Mellitus and diabetic nephropathy combined with gonadal dysfunction.Methods:the serum and testicular tissue of male type 2 diabetes and diabetic nephropathy rats^[1]were divided into three groups:Control Group（NC Group）,type 2 diabetes group（DM Group）,and diabetic nephropathy group（DN group）,three in each group.Serum was collected from-80°C refrigerator for detection of T,FSH and LH.The testis tissue was taken and embedded with paraffin,and the pathological sections were made.The cell morphology of testis in each group was observed after HE staining,and the expression site and positive percentage of Fabp4 and Foxo1 in Testis were observed by immunohistochemistry,the gene expression of FABP4 and FOXO1 in testis was detected by fluorescence quantitative PCR,and the correlation was analyzed by Pearson Correlation Analysis.Results:（1）serum T,LH and FSH were detected by Elisa.T in DM group and DN group was lower than that in NC group（p<0.05）,T in DN group was lower than that in DM group（p<0.05）.LH IN DN group was higher than that in NC group（p<0.05）,LH in DN group was higher than that in DM group（p>0.05）,LH in DM group was higher than that in NC group（p>0.05）.The level of FSH IN DN group was higher than that in DM Group and NC group（p<0.05）,and the level of FSH in DM group was higher than that in NC group（p>0.05）.（2）HE staining of rat testis showed that there were normal testis structure and seminiferous tubules in NC group.In DM group,the basement membrane was abnormal or even ruptured,some seminiferous tubules were atrophied,and the seminiferous tubules were sparse and disordered.In DN Group,the basement membrane was deformed or even ruptured,and there was serious detachment between spermatogenic cells and basement membrane,and the compactness of seminiferous tubules decreased in different degrees.（3）the expression of FABP4 and FOXO1 in rat testis was detected by immunohistochemistry:FABP4 and FOXO1were expressed in rat testis interstitial cells,Sertoli cells and spermatogenic nuclei,the positive percentage of FABP4 in seminiferous tubules of NC group,DM group and DN group was 13%-18%,16%-22%,24%-30%,and the positive percentage of FOXO1 in seminiferous tubules of NC group,DM Group and DN group was 17%-23%,19%-25%,23%-29%respectively.（4）the relative expression of FABP4 IN DN group was higher than that in DM group（p>0.05）and NC group（p<0.05）,and that in DM group was higher than that in NC group（p>0.05）.The relative expression of FABP4 in DN group and DM Group was 2.10 and 1.44 times higher than that in NC group,respectively The relative expression of FOXO1 in DN group was higher than that in DM group（p>0.05）and NC group（p<0.05）,and that in DM group was higher than that in NC group（p>0.05）.The relative expression of FOXO1 in DN group and DM Group was 2.23 and 1.57 times higher than that in NC group.（5）Pearson Correlation Coefficient analysis showed that there was a positive correlation between FABP4 and Foxo1 gene expression in testicular tissues of NC group,DM group and DN group,but the correlation was not significant（p>0.05）.Conclusion:（1）the results of serum sex hormone test showed that the hypogonadism of DM group and DN group was Gonadotropin hypogonadism.（2）the level of FABP4 and FOXO1 gene expression in testis of DM Group and DN group was higher than that of Control Group,suggesting that FABP4 and FOXO1 may be involved in the development of Type 2diabetes mellitus and diabetic nephropathy gonadal dysfunction.（3）FABP4 and FOXO1 in Testis of each group showed positive correlation,but there was no significant difference in correlation.It is suggested that the interaction mechanism between FABP4 and FOXO1 should be further investigated.