Qufeng Tongluo Decoction May Alleviate Podocyte Injury Induced by High Glucose and Hydrogen Peroxide by Regulating Autophagy

Abstract

Background: Diabetic kidney disease is a significant complication of diabetes. Previous studies have confirmed that Qufeng Tongluo (QFTL) decoction can alleviate podocyte injury in a diabetic rat model, but its mechanism remains unclear. The present in vitro study investigated QFTL’s mechanism in protecting podocytes. Methods: The mouse podocyte clone 5 (MPC-5) cell line stimulated by high glucose and hydrogen peroxide was used as a model for podocyte injury. The cells were treated with QFTL, QFTL + SC79 (activator of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and C2 ceramide (inhibitor of the PI3K/Akt). Immunofluorescence, western blot and polymerase chain reaction (PCR) were employed to detect the expression of microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1 (SQSTM1/p62), PI3K, Akt, and phosphatase and tensin homolog (PTEN) proteins and their messenger RNA (mRNA) levels. Results: High glucose and hydrogen peroxide stimulation may disrupt podocytes’ cytoskeletal structure, while QFTL may mitigate these structural changes. After the SC79 intervention, QFTL’s alleviation of the cytoskeletal structure damage disappeared. High glucose and hydrogen peroxide stimulation decreased the expression of LC3 in MPC-5 cells, whereas QFTL upregulated its expression, but this effect was reversed by the SC79 intervention. Interestingly, P62 decreased after high glucose + hydrogen peroxide stimulation, and QFTL failed to upregulate P62. The expression levels of PI3K, Akt, and PTEN in the model group decreased, which were improved by QFTL. Conclusion: These results suggest that QFTL can maintain the stability of autophagic flux in injured podocytes, which may be related to its ability to improve P62 expression but not to regulating the PI3K/Akt signaling pathway.