Suyin Detoxification Prescription Regulates the Klotho and ERK/NF-κB Signaling Pathways to Alleviate Renal Injury.

Abstract

Chronic Kidney Disease (CKD) is an irreversible pathological condition resulting from the gradual accumulation of nephrotoxic substances. The application of the "Kidney Toxicity" theory in CKD treatment holds significant research potential and promising clinical prospects. We established a murine model of unilateral ureteral obstruction (UUO) and administered the traditional Chinese medicine prescription Suyin detoxification prescription (SDP). The efficacy of SDP was assessed by comparing the expression levels of Klotho, NF-κB, pNF-κB, VEGF, α-SMA, pERK1/2, and ERK1/2 proteins with those in the Sham operation group using immunohistochemistry, RT-qPCR, and Western Blot techniques. The study revealed a significant reduction in the expression of Klotho and VEGF proteins during the progression of renal fibrosis in mice, while there was a marked increase in the levels of pNF-κB, α-SMA, and pERK1/2 proteins, demonstrating statistical significance (p < 0.05). In UUO mice treated with a high dose of SDP, these proteins exhibited an opposite expression trend compared to that observed in pure operated model mice, with statistically significant differences (p < 0.05). Subsequently, we investigated the relationship between Klotho protein and the ERK/NF-κB signaling pathway-related proteins in human umbilical vein endothelial cells (HUVECs). Knockdown of Klotho protein in HUVECs confirmed its potential as a target for SDP's renal protective effects in vivo by regulating ERK/NF-κB signaling pathway-related proteins to some extent. The renoprotective effect of SDP is mediated through modulation of Klotho protein expression in renal tissues, thereby influencing the ERK/NF-κB signaling pathway and ameliorating the inflammatory processes associated with renal fibrosis. The present study has significantly contributed to the advancement and refinement of the pathogenesis of "Kidney Toxicity" as well as the therapeutic approach of "Kidney Detoxification".