The Effects of NLRP3 Inflammasome on Intestinal Inflammatory,Injury and JAK/STAT3 Signaling Pathway in Septic Rats
Objective:To investigate the mechanism of nucleotides binding oligomeric domain like receptor protein 3(NLRP3)in-flammasome on the intestinal inflammatory response and intestinal mucosal injury in septic rats through the JAK/STAT3 signaling path-way.Methods:Thirty healthy and clean grade male Wistar rats were chosed and randomly divided into three groups:sham surgery group,model group,and NLRP3 inhibitor group,with 10 rats in each group.The model group and inhibitor group were subjected to cecal liga-tion and perforation for modeling.The inhibitor group was intraperitoneally injected with NLRP3 inhibitor MCC950(10 mg/kg)30 min-utes before modeling,and the model group was injected with equal amount of physiological saline.The 24-hour survival status of rats in each group were observed,ileal pathological score was performed with HE staining,serum tumor necrosis factor-α(TNF-α)and inter-leukin-1β(IL-lβ)were detected using ELISA method,NF-κB p65,NLRP3,apoptosis related spot protein(ASC),aspartate specific cys-teine protease-1(Caspase-1),p-JAK,and p-STAT3 proteins levels in small intestine tissues were detected by Western blot method.Results:① Compared with the sham surgery group,the mortality rate and pathological score of the model group rats significantly increased,serum TNF-α and IL-lβ levels were higher,tissue NF-κB p65,NLRP3,ASC,Caspase-1,p-JAK,and p-STAT3 proteins relative expres-sions were significantly higher,too(P＜0.05).② Compared with the model group,the mortality rate and pathological score of the in-hibitor group rats significantly reduced,serum TNF-α and IL-1 β was significantly lower,levels ofNF-KB p65,NLRP3,ASC,Caspase-1,p-JAK,and p-STAT3 proteins were significantly less,too(P＜0.05).There were still significantly statistical differences between the inhibitor group and the sham surgery group in the above indicators(P＜0.05).Conclusion:NLRP3 inflammasome may enhance the intesti-nal inflammatory response and injury intestinal mucosal in septic rats by activating JAK/STAT3 signaling pathway,targeting intervention of NLRP3 could reverse intestinal injury.
SepsisInflammationNucleotide binding oligomerization domain like receptor protein 3JAK/STAT3 signaling pathway
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