烟碱型乙酰胆碱受体α7激动剂减轻实验性结肠炎炎性反应

目的 探讨烟碱型乙酰胆碱受体α7(nAChRα7)激动剂对三硝基苯磺酸(TNBS)诱导结肠炎的治疗作用.方法 将BALB/C小鼠随机分为对照组(C)、TNBS结肠炎组(T)和nAChRα7激动剂八角枫碱(AN)或拮抗剂二碘四氯吲哚胺(CHD)治疗组.实验第1天诱导(TNBS)结肠炎,实验开始后即对每只小鼠予AN 10μg或CHD 1.5 μg腹腔注射,隔日重复直到实验结束.实验第8天处死小鼠,分别检测肠组织髓过氧化物酶(MPO)活性,酶联免疫吸附试验检测肿瘤坏死因子(TNF)-α浓度,分离结肠黏膜固有层单个核细胞(LPMC),提取核蛋白,Western印迹法检测核因子(NF)-κB P65的表达.结果 AN治疗组结肠组织损伤程度、MPO活性、组织TNF浓度等均明显低于TNBS组MPO活性为(7.6±2.1)U/mg比(12.2±2.6)U/mg,组织TNF浓度为(396±98)pg/g比(627±112)Pg/g],LPMC NF-κB的活化明显受抑制;CHD治疗组结肠组织损伤程度、MPO活性(14.1±1.8)U/mg]、组织TNF浓度(692±79)Pg/g]均明显高于其他结肠炎组,LPMC NF-κB明显活化.结论 nAChR α7激动剂AN能明显抑制实验性结肠炎肠道炎性反应.

Cholinergic receptor nicotinic acetyleholine receptor α7 agonist ameliorates trinitrobenzene sulfonic acid induced colitis in mice

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 decreasedMPO 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.