SIRT1 On Intestinal Function Impairment In Sepsis By Affecting The Activation Of NLRP3 Inflammasome

Objective To investigate whether the activation of silent information regulator 1(SIRT1)can inhibit the activation of nucleotide-binding domain(NOD)-like receptor protein 3(NLRP3)inflammasome in the intestinal injury model of sepsis,so as to improve the intestinal inflammatory response,apoptosis and cell permeability,and play a protective role in intestinal barrier function.Methods Human colorectal adenocellular carcinoma(Caco-2)cells were cultured in vitro,and lipopolysaccharide(LPS)with different concentrations(1μg/ml,2μg/ml,and 4μg/ml)was used for different time(6h,12 h,and 24h)to prepare septic intestinal injury cell model.2μg/ml LPS was used for 12 h to simulate septic intestinal injury model,and RES 10μmol/L,RES 20μmol/L,RES 40μmol/L,and Ex-527 10μmol/L were added for 6h,respectively.Male Wistar rats were selected for cecal ligation and perforation to prepare the animal model of sepsis,and were sacrificed at 6h and 24 h after CLP,respectively.Animals in the RES group were given intraperitoneal injection of 20mg/kg RES at 6h and 12 h after CLP,respectively,and sacrificed at 24 h.Cell viability,inflammatory cytokines,apoptosis,cell permeability,NLRP3,SIRT1,caspase-1and ASC expression levels were detected.Results In the cell model,with the increase of LPS intervention concentration and the extension of intervention time,the activation of NLRP3 inflammasome increased,while SIRT1 was gradually down-regulated.After RES intervention,the level of inflammatory factors decreased,and the cell apoptosis and cell permeability showed a trend of improvement,although there was no statistical difference.RES was used as an SIRT1 agonist to intervene in the injured intestinal model,and the expression level of SIRT1 protein was up-regulated,while the expression of NLRP3 protein and its downstream Caspase-1 and ASC protein were decreased.The expressions of NLRP3 inflammasomes and downstream products Caspase-1 and ASC in intestinal epithelium of RES group rats were significantly decreased.Conclusion Resveratrol,as a SIRT1 agonist,can promote the expression of SIRT1 and inhibit the activation of NLRP3 inflammasome and the expression of downstream molecules when intervening in the injured intestinal model,thus controlling the secretion and release of inflammatory factors and effectively improving the inflammatory response.