Jianpi Qushi Heluo Formula Alleviates Renal Damages in Passive Hemann Nephritis Rats by Upregulating Parkin-Mediated Mitochondrial Autophagy

Abstract Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating membranous nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine(TET), and Benazepril was used as a positive control group. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 hour urinary protein, total cholesterol (TC) and increased serum albumin (ALB). Histology showed that JQHF significant improvements of glomerular hyperplasia, renal tubular damage, IgG immune complex deposition and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF decreasing the level of Reactive Oxygen Species and apoptosis rate, upregulating the level of mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of Parkin and LC3II, and downregulating the expression of Cytochrome c and Cleaved caspase-3 in the kidneys of MN rats. Similarly, TET treatment significantly upregulates the mitochondrial autophagy and decrease the apoptosis of rats after 4 weeks compared with the Model group. Notably, combined with the above results, the ability to alleviates renal damages of JQHF was significantly better than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by Parkin pathways.