Study on the regulatory mechanism of Qingre Quzhuo Capsule on NF-κB/NLRP3 signaling pathway in mice with non-alcoholic steatohepatitis
[Objective]To study the therapeutic effect of Qingre Quzhuo Capsule(QRQZ)on non-alcoholic steatohepatitis(NASH)and impact on the nuclear factor kappa-B(NF-κB)/nucleotide binding oligomerization domain like receptor protein 3(NLRP3)signaling pathway.[Methods]NASH mice were induced by methionine and choline deficiency(MCD)diet and given different doses of QRQZ.Evaluated the therapeutic effect of QRQZ on NASH model mice by detecting body weight,liver index,alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and triglyceride(TC).Hematoxylin-Eosin(HE)and oil red O staining.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)were detected to evaluate the oxidative stress of QRQZ in NASH model mice.Through ELISA,the levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were used to evaluate the effect of QRQZ on the inflammation of NASH mice.By detecting phospho-inhibitor kappa B(P-IκB),phospho-nuclear factor kappa-B(p-NF-κB P65),NLRP3,apoptosine-associated speck-like protein(ASC),cleaved cysteinyl aspartate specific proteinase-1(cleaved Caspase-1),mature The protein level of IL-1β and mRNA expression of NLRP3,ASC,Caspase-1 and IL-1β to evaluate the effect of QRQZ on NF-κB/NLRP3 signaling pathway in NASH mice.[Results]QRQZ can improve the weight loss caused by MCD,decrease liver index,decrease serum ALT,AST activities,TC,TG levels,and improve liver histopathological changes,suggesting that QRQZ has therapeutic effect on NASH model mice.In addition,QRQZ increased the activity of SOD and GSH-Px in liver tissue,decreased the level of MDA,and decreased the levels of IL-6,IL-1β,TNF-α inflammatory factors,suggesting the antioxidant and anti-inflammatory effects of QRQZ.Further studies showed that QRQZ reduced the phosphorylation levels of IκB and P65,and decreased the expression of NLRP3,ASC,Caspase-1,IL-1β protein and gene.These results suggest that QRQZ inhibits the activation of NF-κB/NLRP3 signaling pathway in NASH mice.[Conclusion]QRQZ has therapeutic effect on NASH model mice,and can enhance antioxidant capacity and improve inflammation,the mechanism of which may be related to inhibiting the activation of NF-κB/NLRP3 signaling pathway.
万方数据
维普
