Kupffer cells biomimetic nanoparticles alleviate sepsis related liver injury.

Abstract

The mechanism of sepsis related liver injury (SRLI) is unclear and its treatment method is unsatisfactory. The aim of this study was to investigate the effects of BRCC3 on SRIL and preparation of kupffer cells membrane encapsulated ZIF-8 loaded BRCC3 siRNA (K-EVs@ZIF-8@siRNA) to target BRCC3 to treatment of SRLI. Liver tissues from control mice and SRLI mice were used for RNA sequencing for searching differential genes. The cercal ligation and punchure (CLP) model and lipopolysaccharide (LPS) model were used to evaluate the mechanisms of BRCC3 and the effects of K-EVs@ZIF-8@siRNA on SRLI. The results of RNA-Seq showed BRCC3 and NLRP1were significantly increased in Kuepfer cells of liver tissues of SRLI mice. BRCC3 and NLRP1 have co-localization in Kuepfer cells. It was also found that knock out BRCC3 had protective effects on SRLI via deubiquitylation modification of NLRP1 to inhibit of NLRP1. K-EVs@ZIF-8@siRNA was successfully prepared in this study and exhibited the characteristics of nanoparticles. K-EVs@ZIF-8@siRNA could be enriched in liver tissues and also be absorbed by Kuepfer cells. K-EVs@ZIF-8@siRNA significantly alleviated SRLI by inhibition the BRCC3/NLRP1 signaling pathway. In conclusion, BRCC3 as a key marker was identified in SRLI and K-EVs@ZIF-8@siRNA was successfully prepared for treating SRLI. This study provides a new target and treatment for SRLI.