Abstract:Objective: To investigate the ameliorative effect of Yiqi Yangyin Huoxue Decoction on renal function in rats with membranous nephropathy (MN) through regulating autophagy. Methods: Forty-two SPF male SD rats were randomly divided into a blank group (n=6), a model group (n=9), a benazepril group (n=9), a low-dose Yiqi Yangyin Huoxue Decoction group (n=9), and a high-dose Yiqi Yangyin Huoxue Decoction group (n=9). Except for the blank group, rats in the other groups underwent a single tail vein injection of sheep anti-rat Fx1A serum (6 mL·kg-1) to establish the model. After successful modeling, drug intervention treatment was administered, and each group received corresponding drug administration by gavage for 6 weeks. A fully automated biochemical analyzer was used to measure the levels of 24-hour urinary protein quantitation (24h-UTP), Alb, ALT, AST, BUN, Cr, TC, and TG in the rats. HE and PASM staining were performed to observe the pathological changes in the renal tissue of the rats. Western Blot was used to detect the expression level of Nephrin protein in the renal tissue of the rats. Western Blot and qPCR were used to detect the expression levels of SIRT1, FoxO3, BNIP3, LC3I, and LC3II proteins and mRNA in the renal tissue of the rats. Results: Compared with the blank group, the model group exhibited significantly elevated 24h-UTP levels (P<0.01), significantly reduced Alb levels, and significantly elevated BUN, Cr, TC, and TG levels (P<0.01). The glomerular basement membrane thickened, the expression level of Nephrin protein decreased, and the expression levels of SIRT1, FoxO3, BNIP3 proteins and mRNA significantly decreased (P<0.01). Compared with the model group, the 24h-UTP levels in each treatment group were significantly reduced (P<0.01), Alb levels were significantly elevated, and BUN, Cr, TC, and TG levels were significantly decreased (P<0.01). The pathological damage in the renal tissue showed varying degrees of improvement, the expression level of Nephrin protein increased, and the expression levels of SIRT1, FoxO3, BNIP3, and LC3II/I proteins and mRNA significantly increased (P<0.01). Conclusion: Yiqi Yangyin Huoxue Decoction may enhance autophagy by activating the SIRT1/FoxO3/BNIP3 pathway, thereby improving the renal pathological state in MN rats and exerting a protective effect on the kidneys.