PROTECTIVE EFFECT OF INHIBITING NLRP3 INFLAMMASOME ON LIVER FUNCTION IN RATS WITH ACUTE LIVER FAILURE

Pengxiang Wang¹, Weiming Yu¹, Yiyu He^{2, *, #}, Likun Wang^{3, *, #} 

¹Weifang Medical University, Weifang, Shandong, 261000, China - ²Department of Cardiovascular Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China - ³Department of infection control center, Linyi people's hospital, Linyi, Shandong 276000, China

Introduction: This paper was aimed at exploring the role of NLRP3 in acute hepatic failure (AHF) and the impact of inhibiting NLRP3 on liver function

Materials and methods: Sixty SPF Wistar rats were stochastically assigned into Model group (MG), Intervention group (IG) and Control group (CG). AHF modeling was performed in MG and IG, and IG was injected with MCC950, a specific inhibitor of the NLRP3 Inflammasome, through tail vein 4 h before modeling. NLRP3 mRNA, interleukin (IL)-1β, IL-18, oxidative stress response (OSR) and liver fibrosis (LF) process of rats in each group were tested upon the completion of modeling. All rats were killed 24 h after modeling, to observe the liver tissue by HE staining, detect hepatocyte activity by flow cytometry, and measure the NLRP3/Caspase-1/IL-1β axis in liver tissue.

Results: In MG, edema, degeneration, and necrosis were observed in disorganized hepatocytes, hepatic cords were disordered, and inflammatory cells and fibrous tissue were infiltrated and proliferated in large quantities, accompanied by hepatic sinusoidal dilatation and congestion. IG showed evidently reduced NLRP3 mRNA, IL-1β and IL-18, inhibited OSR and LF, and increased liver function than MG after modeling (all P<0.05). In comparison with IG, the apoptosis rate and Bax protein of hepatocytes in MG were higher, Bcl-2 protein was lower, and NLRP3, Caspase-1 and IL-1β protein were all increased (all P<0.05).

Conclusions: Inhibition of the NLRP3 inflammasome can validly reduce inflammation, OSR, LF and hepatocyte apoptosis in AHF rats, and facilitate the recovery of liver function, which may be related to the NLRP3/Caspase-1/IL-1β axis.