Effect of Curcumol on NOD-Like Receptor Thermoprotein Domain 3 Inflammasomes in Liver Fibrosis of Mice

Objective:To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3(NLRP3)inflammasomes,and analyze the mechanism underlying curcumol against liver fibrosis.Methods:Thirty Kunming mice were divided into a control group,a model group and a curcumol group according to a random number table,10 mice in each group.Mice were intraperitoneally injected with 40% carbon tetrachloride(CCl4:peanut oil,2:3 preparation)at 5 m L/kg for 6 weeks,twice a week,for developing a liver fibrosis model.The mice in the control group were given the same amount of peanut oil,twice a week for 6 weeks.The mice in the curcumol group were given curcumol(30 m L/kg)intragastrically,and the mice in the model and control groups were given the same amount of normal saline,once a day for 6 weeks.Changes in liver structure were observed by hematoxylin and eosin(HE)and Masson staining.Liver function,liver fiber indices,and the expression of interleukin(IL)-10 and tumor necrosis factor-α(TNF-α)levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit.Immunoblotting and reverse transcription-quantitative PCR(RT-qPCR)were performed to detect the expression of NLRP3 inflammasome-related molecules,TGF-β and collagen.Results:HE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition.The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group(P<0.05);RT-qPCR and Western blot results reveal that,in the curcumol group,the mRNA and protein expression levels of NLRP3,IL-1β,Caspase 1 and gasdermin D decreased significantly compared with the model group(P<0.05);immunohistochemical results showed that in the curcumol group,the protein expression levels of NLRP3 and IL-1β decreased significantly compared with the model group(P<0.05).Conclusion:A potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.