NLRP3 炎症小体对脓毒症大鼠肠道炎症与损伤及 JAK/STAT3 信号通路的影响.

Objective: To investigate the mechanism of nucleotides binding oligomeric domain like receptor protein 3 (NLRP3) inflammasome on the intestinal inflammatory response and intestinal mucosal injury in septic rats through the JAK/STAT3 signaling pathway. 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 ligation and perforation for modeling. The inhibitor group was intraperitoneally injected with NLRP3 inhibitor MCC950 (10 mg/kg) 30 minutes 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 interleukin-1β (IL-1β) were detected using ELISA method, NF-κB p65, NLRP3, apoptosis related spot protein (ASC), aspartate specific cysteine 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-1β levels were higher, tissue NF-κB p65, NLRP3, ASC, Caspase-1, p-JAK, and p-STAT3 proteins relative expressions were significantly higher, too (P<0.05). ② Compared with the model group, the mortality rate and pathological score of the inhibitor group rats significantly reduced, serum TNF-α and IL-1β was significantly lower, levels of NF-κB 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 intestinal inflammatory response and injury intestinal mucosal in septic rats by activating JAK/STAT3 signaling pathway, targeting intervention of NLRP3 could reverse intestinal injury. [ABSTRACT FROM AUTHOR]