Hirudin Alleviates Renal Fibrosis by Inducing Autophagy to Suppress NLRP3 Inflammasome Activation

Renal fibrosis is a pathological feature of chronic kidney injury that contributes to renal failure. This study aimed to explore the effect of Hirudin on renal fibrosis. The anti-fibrotic effect of Hirudin was evaluated using unilateral ureteral obstruction (UUO) rats and TGF-β-treated HK-2 cells. The Autophagy inhibitor 3-Methyladenine was used to further explore the potential mechanism. Hirudin treatment significantly reduced UUO-induced elevations in blood urea nitrogen, creatinine, and alpha-smooth muscle actin (α-SMA) levels, and improved kidney injury and renal fibrosis. In addition, Hirudin markedly decreased NLRP3 inflammasome-related protein expression and increased autophagy-related protein expression in the kidneys of UUO rats. Hirudin significantly increased cell viability, reduced α-SMA and NLRP3 inflammasome-related protein levels, and increased autophagy-related protein levels in TGF-β-treated HK-2 cells. However, the effects of Hirudin were counteracted by 3-Methyladenine. In conclusion, Hirudin inhibits the activation of NLRP3 inflammasome by inducing Autophagy to improve renal fibrosis.

Hirudin; NLRP3; autophagy; inflammasome; renal fibrosis.