Cholinergic receptor nicotinic acetyleholine receptor α7 agonist ameliorates trinitrobenzene sulfonic acid induced colitis in mice / 中华消化杂志

ABSTRACT

Objective To study the therapeutic effect of cholinergie receptor,an nicotinic acetylcholine receptor(nAChR)α7 agonist,on trinitrobeazene sulfonic acid(TNBS)-induced colitis in mice.Methods BALB/C mice were randomly divided into control group,TNBS group,anabaseine(AN)as the agonist of nAChRα7(AN group),and chlorisondamine diiodide(CHD)as the antagonist of nAChRα7(CHD group).TNBS-induced colitis was produced at day 1,either 10 μg anabaseine or 1.5 μg chlorisondamine diiodide was administrated after the induction of colitis,and repeated on interval day till the mice were sacrificed at day 8.The myeloperoxidase(MPO)activity and level of tumor necrosis factors(TNF)-α in colonic tissue were examined by histological method and enzyme-linked immunosorbent assay (ELISA),respectively.Lamina propria mononuclear cells(LPMCs)were isolated,and NF-κB activation was further detected by Western blot.Results Compared with TNBS group,the tissue damage,MPO activity and concentration of TNF-α in mice treated with anabaseine were decreased[MPO activity(7.6±2.1)U/mg vs(12.2±2.6)U/mg,TNF-α level(396±98)pg/g vs(627±112)Pg/g],and NF-κB activation in LPMCs was inhibited.Whereas the MPO activity[(14.1±1.8) U/mg)]and concentration of TNF-α[(692±79)pg/g)]in mice treated with chlorisondamine diiodide were increased and NF-κB activation in LPMCs were amplified. Conclusion nAChRa7 agonist can inhibit colonic inflammatory response by down-regulating the consentration of TNF-α and inhibiting NF-κB activation.