Protective Effect Of Auxiliary Hypoglycemic Tablets On Renal Function In Type 2 Diabetic KKAy Mice And Its Mechanism

Objective:The aim of our animal study was to investigate the protective effects and part of their underlying mechanism of Fuzhujiangtang Granules (FT-5) and the combination of FT-5 and Irbesartan (FT-5+IRB) on the kidney of type 2 diabetes KKAy mices, which was able to provide the basis for clinical application.Methods:Twenty four eighteen-week-old female KKAy mice were randomly divided in vehicle group, FT-5 group, FT-5+IRB group and irbesartan(IRB) group, while 6 female C57BL/6J mice were used as normal control. We measured body weight (BW) and fasting blood glucose (FBG). At the end of the experiment, all surviving mice were sacrificed. The serum lipid, the serum renal parameters, the 24 h albuminuria were measured, and the renal morphology including HE, Masson, PAS were observed. To search the underlying mechanism, we measured the expression of slit diaphragm protein nephrin mRNA by real-time fluorescent quantitative polymerase chain reaction (RT-PCR), and the number of podocytes by immunohistochemical staining for podocyte positive marker—WT-1.Results:After 8-week treatment, FT-5 and FT-5+IRB treatments significantly alleviated the increase of 24 h albuminuria, and improved glomerular mesangial proliferation, and basement membrane thickening lesions. In addition, FT-5 and FT-5+IRB increased the expression of nephrin mRNA and the number of podocytes in the KKAy mices, mitigated podocyte lesions to prevent the progression of DN.Conclusion:Fuzhujiangtang Granules and the combination of FT-5 and Irbesartan protect podocyte in the kidney of diabetic KKAy mice. These treatments significantly improved the expression of SD molecules nephrin and the number of podocytes, alleviated the podocyte lesion and glomerular pathologic changes, which resulted in the decrease of albuminuria. These finding suggest that FT-5 and FT-5+IRB mitigate the renal lesion in KKAy mice, and protect the podocyte from the development of DN via upregulaing slit diaphragm molecules expression and the number of podocytes.