Molecular mechanism of propofol in reducing kidney injury induced by autologous orthotopic liver transplantation.

Abstract

OBJECTIVE: This study explores the mechanism of propofol in autologous orthotopic liver transplantation (AOLT)-insulted kidney injury. METHODS: A rat model of OALT-induced kidney injury was established, followed by intraperitoneal injection of propofol. Rat renal tubular epithelial cells (RTECs) were induced by hypoxia/reoxygenation. Renal pathological changes were observed via H&E and PAS staining. TNF-α, IL-8, IL-6, IL-1β, and IL-18 levels were measured via ELISA. NLRP3, cleaved Caspase-1, and GSDMD-N expressions were tested via Western blot. The binding of SIRT1 to FOXO3a, SIRT1 to ASC, and ASC to NLRP3, as well as acetylation levels of FOXO3a, ASC, and NLRP3 were analyzed via immunoprecipitation. The binding between FOXO3a and ASC was verified via Ch-IP and dual luciferase assays. RESULTS: SIRT1 expression is augmented in rat kidney tissues following AOLT, and propofol further elevates SIRT1 expression. Propofol alleviates AOLT-induced kidney injury and pyroptosis. Mechanistically, SIRT1 binds to FOXO3a in the nucleus to inhibit its acetylation, thereby reducing ASC expression. Moreover, SIRT1 binds to ASC in the cytoplasm to inhibit its acetylation, thereby inhibiting the binding of ASC to NLRP3. CONCLUSION: In conclusion, Propofol promotes SIRT1-mediated deacetylation to inhibit RTEC pyroptosis via FOXO3a/ASC/NLRP3 axis and alleviate AOLT-induced kidney injury.