半夏泻心汤对溃疡性结肠炎小鼠肠道黏膜屏障功能保护作用及ZO-1和Occludin表达的影响
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摘要
目的:观察半夏泻心汤对溃疡性结肠炎(UC)小鼠肠道黏膜屏障功能的保护作用并探讨其可能的作用机制。方法:建立三硝基苯磺酸(TNBS)诱导小鼠实验性溃疡性结肠炎模型,实验按随机数字表法分为正常对照组、模型组、半夏泻心汤4. 5 g/kg组、半夏泻心汤9. 0 g/kg组和阳性对照组,连续给药21 d后考察小鼠DAI变化,测量结肠长度并进行CMDI及HS评分,测定MPO活性、DAO及D-LA水平、L/M值,检测ZO-1和Occludin的表达。结果:与正常对照组比较,模型组DAI、CMDI、HS、MPO活性、D-LA和DAO水平、L/M值明显升高,结肠长度ZO-1和Occludin表达明显降低;与模型组比较,半夏泻心汤4. 5 g/kg组、半夏泻心汤9. 0 g/kg组及阳性对照组DAI、CMDI、HS、MPO活性、D-LA和DAO水平、L/M值明显降低,结肠长度ZO-1和Occludin表达明显升高。结论:半夏泻心汤可能通过升高ZO-1和Occludin表达,从而保护溃疡性结肠炎小鼠肠道黏膜的屏障功能。
Objects: To investigate the protective effect of the Banxia Xiexin decoction on the intestinal mucosal barrier in the treatment of ulcerative colitis( UC),and also to explore the possible mechanism involved.Methods: Ulcerative colitis models were induced by rectal instillation with TNBS.BALB/c mices were randomly divided into the normal control group,the model group,the Banxia Xiexin decoction 4. 5 g/kg group,the Banxia Xiexin decoction 9. 0 g/kg group and the positive control group. After 21 consecutive days,DAI was investigated during the drug treatment,the colon sample were collected after drug administration for evaluating the colon length,CMDI and HS,the MPO activities,the DAO and the D-LA levels,L/M value,the expressions of ZO-1 and Occludin were measured. Results: Compared with the normal control group,DAI,CMDI,HS,the MPO activities,the DAO and the D-LA levels as well as the L/M value in the model group increased significantly,the colon length,the expressions of ZO-1 and Occludin in model group reduced significantly; Compared with the model group,DAI,CMDI,HS,the MPO activities,the DAO and the D-LA levels as well as the L/M value increased significantly in the Banxia Xiexin decoction 4. 5 g/kg group,the Banxia Xiexin decoction 9. 0 g/kg group and the positive control group,the colon length,the expressions of ZO-1 and Occludin reduced significantly in the the Banxia Xiexin decoction 4. 5 g/kg group,the Banxia Xiexin decoction 9. 0 g/kg group and the positive control group. Conclusion: The Banxia Xiexin decoction play a protective effects on intestinal mucosal barrier function in mices with ulcerative colitis by increasing the expressions of ZO-1 and Occludin.
Objects: To investigate the protective effect of the Banxia Xiexin decoction on the intestinal mucosal barrier in the treatment of ulcerative colitis( UC),and also to explore the possible mechanism involved.Methods: Ulcerative colitis models were induced by rectal instillation with TNBS.BALB/c mices were randomly divided into the normal control group,the model group,the Banxia Xiexin decoction 4. 5 g/kg group,the Banxia Xiexin decoction 9. 0 g/kg group and the positive control group. After 21 consecutive days,DAI was investigated during the drug treatment,the colon sample were collected after drug administration for evaluating the colon length,CMDI and HS,the MPO activities,the DAO and the D-LA levels,L/M value,the expressions of ZO-1 and Occludin were measured. Results: Compared with the normal control group,DAI,CMDI,HS,the MPO activities,the DAO and the D-LA levels as well as the L/M value in the model group increased significantly,the colon length,the expressions of ZO-1 and Occludin in model group reduced significantly; Compared with the model group,DAI,CMDI,HS,the MPO activities,the DAO and the D-LA levels as well as the L/M value increased significantly in the Banxia Xiexin decoction 4. 5 g/kg group,the Banxia Xiexin decoction 9. 0 g/kg group and the positive control group,the colon length,the expressions of ZO-1 and Occludin reduced significantly in the the Banxia Xiexin decoction 4. 5 g/kg group,the Banxia Xiexin decoction 9. 0 g/kg group and the positive control group. Conclusion: The Banxia Xiexin decoction play a protective effects on intestinal mucosal barrier function in mices with ulcerative colitis by increasing the expressions of ZO-1 and Occludin.
引文
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[6]黄婧渝,农辉,裴羡,等.四君子汤对溃疡性结肠炎小鼠模型肠黏膜屏障的作用机制[J].世界华人消化杂志,2015,23(27):4326-4334.
[7]杨贵珍,郑月娟,姜昕,等.半夏泻心汤抑制巨噬细胞分泌促炎因子抗胃炎机制研究[J].中国中西医结合消化杂志,2015,23(3):160-164.
[8]王江,周永学,谢勇波,等.半夏泻心汤拆方对胃溃疡大鼠胃组织GAS、MTL与血清PAF、ET、NO的影响及其寒热并用配伍的意义研究[J].中华中医药学刊,2016,34(11):2776-2779.
[9]张海燕.半夏泻心汤治疗溃疡性结肠炎40例临床研究[J].亚太传统医药,2016,12(2):109-110.
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[12] LUKE HH,KO JKS,FUNG HS,et al.Delineation of the protectiveaction of zinc sulfate on ulcerative colitis[J]. Eur J Pharmacol,2002,443:197-204.
[13] ALIPOUR M,ZAIDI D,VALCHEVA R,et al. Mucosal BarrierDepletion and Loss of Bacterial Diversity are PrimaryAbnormalities in Paediatric Ulcerative Colitis[J]. J CrohnsColitis,2016,10(4):462-471.
[14]臧凯宏,吴建军,秦红岩,等.黄芪多糖对溃疡性结肠炎大鼠肠道黏膜屏障的影响[J].中药材,2017,40(1):208-211.
[15]叶毅君,陆虞荪,周雪,等.针刺对5-氟尿嘧啶所致肠黏膜屏障破坏大鼠的保护作用[J].针刺研究,2016,41(2):95-99.
[16]江学良,崔慧斐,任晶,等.思密达治疗溃疡性结肠炎腹泻的机制和疗效[J].中国全科医学,2011,14(6c):2031-2033.
[17]顾鉴秋,邵梦茹,陈家艺,等.肠炎清口服液改善小鼠溃疡性结肠炎肠道黏膜通透性的作用机制[J].中国实验方剂学杂志,2014,20(23):133-137.
[18] HENDERSON P,VAN LIMBERGEN J E,SCHWARZE J,et al.Function of the intestinal epithelium and its dysregulation ininflammatory bowel disease[J]. Inflamm Bowel Dis,2011,17(1):382-395.
[19]姜宗丹,张振玉,孔超美,等.美沙拉嗪对溃疡性结肠炎患者肠黏膜紧密连接蛋白表达的影响[J].胃肠病学,2013,18(8):462-464.
[20]申发燕,张声.紧密连接蛋白ZO-1 PDZ结构域的研究进展[J].湖北民族学院学报:医学版,2012,29(3):62-65.
[2]赵红伟,岳月红,郎晓猛,等.PolyⅠ:C对急性期溃疡性结肠炎小鼠肠黏膜屏障的影响[J].重庆医学,2017,46(3):299-301.
[3] MATUSIEWICZ M,NEUBAUER K,BEDNARZ-MISA I,et al.Systemic interleukin-9 in inflammatory bowel disease:Association with mucosal healing in ulcerative colitis[J].World JGastroenterol,2017,23(22):4039-4046.
[4] HORIO Y,UCHINO M,BANDO T,et al.Rectal-sparing type ofulcerative colitis predicts lack of response to pharmacotherapies[J].BMC Surg,2017,17(1):59.
[5] MA TM,XU N,MA XD,et al.Moxibustion regulates inflammatorymediators and colonic mucosal barrier in ulcerative colitis rats[J].World J Gastroenterol,2016,22(8):2566-2575.
[6]黄婧渝,农辉,裴羡,等.四君子汤对溃疡性结肠炎小鼠模型肠黏膜屏障的作用机制[J].世界华人消化杂志,2015,23(27):4326-4334.
[7]杨贵珍,郑月娟,姜昕,等.半夏泻心汤抑制巨噬细胞分泌促炎因子抗胃炎机制研究[J].中国中西医结合消化杂志,2015,23(3):160-164.
[8]王江,周永学,谢勇波,等.半夏泻心汤拆方对胃溃疡大鼠胃组织GAS、MTL与血清PAF、ET、NO的影响及其寒热并用配伍的意义研究[J].中华中医药学刊,2016,34(11):2776-2779.
[9]张海燕.半夏泻心汤治疗溃疡性结肠炎40例临床研究[J].亚太传统医药,2016,12(2):109-110.
[10]赵效国.新编医学动物实验设计与方法[M].北京:科学出版社,2009:79-80.
[11]臧凯宏,姚旭芳,任远,等.当归补血汤对溃疡性结肠炎大鼠肠道黏膜屏障功能的影响[J].中国临床药理学杂志,2016,32(10):905-908.
[12] LUKE HH,KO JKS,FUNG HS,et al.Delineation of the protectiveaction of zinc sulfate on ulcerative colitis[J]. Eur J Pharmacol,2002,443:197-204.
[13] ALIPOUR M,ZAIDI D,VALCHEVA R,et al. Mucosal BarrierDepletion and Loss of Bacterial Diversity are PrimaryAbnormalities in Paediatric Ulcerative Colitis[J]. J CrohnsColitis,2016,10(4):462-471.
[14]臧凯宏,吴建军,秦红岩,等.黄芪多糖对溃疡性结肠炎大鼠肠道黏膜屏障的影响[J].中药材,2017,40(1):208-211.
[15]叶毅君,陆虞荪,周雪,等.针刺对5-氟尿嘧啶所致肠黏膜屏障破坏大鼠的保护作用[J].针刺研究,2016,41(2):95-99.
[16]江学良,崔慧斐,任晶,等.思密达治疗溃疡性结肠炎腹泻的机制和疗效[J].中国全科医学,2011,14(6c):2031-2033.
[17]顾鉴秋,邵梦茹,陈家艺,等.肠炎清口服液改善小鼠溃疡性结肠炎肠道黏膜通透性的作用机制[J].中国实验方剂学杂志,2014,20(23):133-137.
[18] HENDERSON P,VAN LIMBERGEN J E,SCHWARZE J,et al.Function of the intestinal epithelium and its dysregulation ininflammatory bowel disease[J]. Inflamm Bowel Dis,2011,17(1):382-395.
[19]姜宗丹,张振玉,孔超美,等.美沙拉嗪对溃疡性结肠炎患者肠黏膜紧密连接蛋白表达的影响[J].胃肠病学,2013,18(8):462-464.
[20]申发燕,张声.紧密连接蛋白ZO-1 PDZ结构域的研究进展[J].湖北民族学院学报:医学版,2012,29(3):62-65.