Yiqi Qingre Xiaozheng formula protects against diabetic nephropathy by restoring autophagy in mice

Objective:To evaluate the protective effect of Yiqi Qingre Xiaozheng formula(YQQRXZF)via the regulation of autophagy in diabetic nephropathy(DN)mice induced by injection of streptozotocin(STZ)after high fat diet(HFD).Methods:The composition of YQQRXZF was analyzed by high performance liquid chromatographyelectrospray ionization/mass spectrometry(HPLC-ESI/MSn).The DN model was induced by intraperitoneally injection of 50 mg/kg STZ within 5 days,followed by HFD feeding for 8 weeks in C57BL/6J mice.Mice were randomly separated into DN group,YQQRXZF group,irbesartan group,and control group.Blood glucose was calculated,and body weight was measured every 2 weeks.An enzyme-linked immunosorbent assay was used to measure the urinary albumin-to-creatinine ratio(uACR)before and after treatment,and the serum concentrations of total cholesterol(TC),low-density lipoprotein(LDL),triglycerides(TG),high-density lipoprotein(HDL),blood urea nitrogen(BUN),and serum creatinine(Scr)were measured.In addition,hematoxylin-eosin(H&E)staining,periodic acid-Schiff(PAS)staining,Masson's trichrome staining,and transmission electron microscopy(TEM)were used to observe pathological changes in renal tissue.Autophagy levels were determined by immunofluorescence staining.Results:In this study,21 dominant chemical constituents were identified in YQQRXZF.The treatment group reduced u ACR in a more significant way than the DN group(P=.018).The treatment group reduced TC,TG,and LDL concentrations after YQQRXFF treatment(P=.021,P=.014 and P=.026,respectively).H&E,PAS,and Masson staining showed that pathological damage to mice kidneys improved,the volume of renal glomeruli was reduced,and glomerular sclerosis and fibrosis were reduced.Immunofluorescence analysis revealed that expressions of LC3-Ⅱprotein increased in the treatment group(P=.013).In contrast,the protein expressions of P62 were reduced after treatment(P=.025).