脱氧胆酸促进肠道组织产生IL-1β及诱导肠道炎症作用的研究  

Study of deoxycholic acid on the production of IL-1β and induction of intestinal inflammation

作　　者：赵胜男[1,2] 龚自珍[1,2] 周洁菲 吴瑾[1,2] ZHAO Sheng-nan;GONG Zi-zhen;ZHOU Jie- fei;WU Jin(Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200092, China;Shanghai Institute for Pediatric Research,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院,上海200092 [2]上海市儿科医学研究所,上海200092

出　　处：《东南大学学报（医学版）》2017年第2期171-176,共6页Journal of Southeast University(Medical Science Edition)

基　　金：上海市自然科学基金资助项目(16ZR1428500)

摘　　要：目的:研究高脱氧胆酸(DCA)对肠道促炎因子IL-1β等的表达及肠道炎症的诱导作用。方法:给予小鼠添加DCA的膳食,建立小鼠肠道高DCA模型,采用HE染色观察小鼠肠道病理损伤情况;以Western Blot检测结肠组织成熟IL-1β的产生;以实时PCR检测IL-6、MCP-1的表达水平;通过髓过氧化物酶(MPO)活力检测肠道炎症情况。结果:给予小鼠添加0.2%DCA的膳食3个月后,其结肠长度明显缩短[对照组(8.1±0.5)cm vs DCA组(7.3±0.3)cm,P<0.01];代表肠道炎症程度的指标MPO活性显著上升[对照组(1.6±0.4)U·g^(-1)vs DCA组(3.0±0.5)U·g^(-1),P<0.01];HE染色可见结肠黏膜破损,黏膜下水肿及炎症细胞浸润。同时DCA膳食可明显诱导结肠组织成熟IL-1β的产生,并导致促炎因子IL-6(对照组1.0±0.1 vs DCA组174.6±45.9,P<0.01)及髓系趋化因子MCP-1(对照组1.0±0.1 vs DCA组187.8±26.2,P<0.001)的mRNA水平表达显著升高。结论:高水平DCA可诱导肠道炎症发生,激活炎症小体、促进成熟IL-1β产生可能是其重要作用机制之一。O bjective:To investigate the effect of high level deoxycholic a0d(DCA)on the intestinal inflammation occurrence.M ethods:Mice were\d with routine diet supplemented with0.2%DCA,HEstaining was performed to observe intestinal pathological injury;Western Blot and Realtime PCR detect mature IL-1!production and IL-6,MCP-1expression respectively;intestinal inflammation was assessed bythe measurement of MP0activity.Results%Mice fed the DCA-supplemented diet developed obvious intestinal in-flammation and injury#as evidenced by significant shortening of colon lengtli&control group DCAgroup(7.3±0.3)cm,p<0.01]and much higher MPO activity[control group(1.6±0.4)U*s12DCAgroup(3.0±0.5)U*g_1,p<0.01];HE staining of colonic tissue in DCA group showed intestinal mucosal impairment,submucosal edema and inflammatory cell infiltration.Of note,the mature IL_1p level in colon tissue waselevated dramatically in DCA-ed group.Meanwhile,the mRNA levels of IL_6(control group1.0±0.1v DCAgroup174.6±45.9,!<0?01)and MCP-1(control group1?0±0?1v DCAgroup187.8±26.2,p<0.001)inDCA group were significantly increased as well.Conclusion:High level DCA can induce the occurrence of intestinalinflammation,which may at least partially depend on the activation of inflammasome and production of IL_1p.

关 键 词：炎症性肠病 脱氧胆酸 白细胞介素1β炎症小体 小鼠 

分 类 号：R574.62[医药卫生—消化系统]