Mechanism of Faecalibacterium prausnitzii in Treating TNBS-induced Colitis in Rats / 胃肠病学

ABSTRACT

Background:NLRP3 inflammasome attracts widespread attention in study of inflammatory bowel disease. Faecalibacterium prausnitzii(Fp)is an anti-inflammatory commensal bacterium that has preventive and therapeutic effects on rat colitis. Aims:To explore the underlying mechanism of Fp in treating experimental colitis in rats. Methods:Fifty rats were randomly divided into two groups,10 in control group and 40 in model group. Rats in model group were administered intrarectally with 5% TNBS and dehydrated alcohol to induce experimental colitis. Twenty-four hours afterwards,the model rats were further divided into four groups and administered intragastrically with PBS,culture medium,live Fp and Fp supernatant 1 mL per day,respectively,for 7 days. On day 8,all the rats were sacrificed for evaluation of colonic inflammation. Expressions of the constituents of NLRP3 inflammasome(NLRP3,ASC,and caspase-1)were assessed by Western blotting and real-time PCR;levels of IL-1β and IL-18,the downstream effectors of NLRP3 inflammasome,in colon and plasma were measured by real-time PCR and ELISA,respectively. Results:Weight loss, reduced colon length and colonic inflammatory injury were observed in model rats. These manifestations were ameliorated in live Fp and Fp supernatant groups than those in PBS and culture medium groups. In PBS and culture medium groups, expressions of NLRP3,ASC,and caspase-1 protein and mRNA in colonic tissue were significantly higher than those in control group(P < 0. 05),the colonic and plasma levels of IL-1β were increased(P < 0. 05),and IL-18 levels were decreased(P < 0. 05). In live Fp and Fp supernatant groups,IL-18 level showed a further reduction as compared with PBS and culture medium groups( P < 0. 05),but the increasing trend for other parameters was reduced( P < 0. 05). Conclusions:NLRP3 inflammasome participates in the development of TNBS-induced colitis in rats. Fp might alleviate colonic inflammation by inhibiting NLRP3 inflammasome and its downstream effectors.