肠泰胶囊改善三硝基苯磺酸诱导的小鼠实验性结肠炎的作用及其机制研究
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摘要
目的:观察肠泰胶囊改善三硝基苯磺酸(TNBS)诱导的小鼠实验性结肠炎的作用及其初步的机制。方法:小鼠麻醉后直肠内灌注100μL含1.5mg TNBS的50%乙醇溶液制备结肠炎模型。造模后第2天开始给予肠泰胶囊,连续8d。观察小鼠的DAI评分、结肠组织学、结肠MPO活性、结肠黏膜糖原PAS染色及细胞因子IL-12/23 p40和IFN-γ的表达。结果:肠泰胶囊改善TNBS结肠炎小鼠的DAI评分(P<0.05),并能缓解结肠局部的炎症,改善结肠黏膜杯状细胞的分泌,减轻组织中炎性细胞的浸润,显著抑制结肠组织中IL-12/23 p40和IFN-γ的表达(P<0.01,P<0.05)。结论:肠泰胶囊对TNBS诱导的小鼠结肠炎具有明显的防治作用,其机制与抑制Th1反应有关。
Objective: To explore effects of Changtai Capsule on experimental colitis induced by trinitrobenzene sulfonic acid(TNBS) in mice. Methods: TNBS colitis was induced by 100μL rectal administration of 1.5 mg trinitrobenzene sulfonic acid in 50% ethanol. Changtai Capsule was administered on the 2 nd day after the establishment of the model for 8 consecutive days.Changes in disease activity index(DAI) together with histological scores were evaluated, and myeloperoxidase(MPO) in colonic tissue was detected, and Periodic Acid-Schiff(PAS) stain in colonic tissue was analyzed, and the production of IL-12/23 p40 and IFN-γ secreted in colonic tissue were determined with ELISA. Results: Changtai Capsule treatment significantly reduced DAI and histological scores of TNBS colitis in mice(P<0.05), it also alleviated neutrophil infiltration of colonic tissue in the model and improved the expression and secretion of goblet cells in colon mucosa. TNBS colitis mice have higher production of IL-12/23 p40 and IFNγ than that of control group, and Changtai Capsule suppress the secretion of IL-12/23 p40 and IFN-γ(P<0.01, P<0.05).Conclusion: Changtai Capsule has obvious preventive and therapeutic effects on TNBS-induced colitis in mice, and its mechanism is related to the inhibition of Th1 reaction.
Objective: To explore effects of Changtai Capsule on experimental colitis induced by trinitrobenzene sulfonic acid(TNBS) in mice. Methods: TNBS colitis was induced by 100μL rectal administration of 1.5 mg trinitrobenzene sulfonic acid in 50% ethanol. Changtai Capsule was administered on the 2 nd day after the establishment of the model for 8 consecutive days.Changes in disease activity index(DAI) together with histological scores were evaluated, and myeloperoxidase(MPO) in colonic tissue was detected, and Periodic Acid-Schiff(PAS) stain in colonic tissue was analyzed, and the production of IL-12/23 p40 and IFN-γ secreted in colonic tissue were determined with ELISA. Results: Changtai Capsule treatment significantly reduced DAI and histological scores of TNBS colitis in mice(P<0.05), it also alleviated neutrophil infiltration of colonic tissue in the model and improved the expression and secretion of goblet cells in colon mucosa. TNBS colitis mice have higher production of IL-12/23 p40 and IFNγ than that of control group, and Changtai Capsule suppress the secretion of IL-12/23 p40 and IFN-γ(P<0.01, P<0.05).Conclusion: Changtai Capsule has obvious preventive and therapeutic effects on TNBS-induced colitis in mice, and its mechanism is related to the inhibition of Th1 reaction.
引文
[1]杨佳,范恒.复方苦参汤对溃疡性结肠炎大鼠炎性反应和氧化应激的影响.中华中医药杂志,2017,32(8):3457-3461
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[11]徐连登,张宇霞,郑献敏.四神丸合四逆散治疗溃疡性结肠炎42例临床观察.吉林中医药,2012,32(5):483-484
[12]王玉珏.加味香连丸治疗溃疡性结肠炎63例.云南中医中药杂志,2010,31(4):86-87
[13]程虹,蒋巧俐,吴东方.青藤碱对TNBS诱导的慢性小鼠结肠炎的治疗作用.中国药师,2017,20(3):449-452
[14]陈东,王建民,李明,等.肠愈灌肠方对溃疡性结肠炎大鼠炎症相关因子及DOR、β-arrestin1、Bcl-2表达影响.中医药临床杂志,2017,29(1):90-94
[15]徐洋洋,蔡皓,段煜,等.白术芍药散治疗溃疡性结肠炎研究进展.中国中药杂志,2017,42(5):856-862
[16]Janek V,Kiyokazu K,Manjit B,et al.Reciprocal regulation ofsubstance P and IL-12/IL-23 and the associated cytokines, IFNγ/IL-17:A perspective on the relevance of this interaction to multipleSclerosis.Journal of Neuroimmune Pharmacology,2015,10:457-467
[17]P J Morrison,S J Ballantyne,M C Kullberg.Interleukin-23 and Thelper 17-type responses in intestinal inflammation:From cytokinesto T-cell plasticity.Immunology,2011,133:397-408
[18]Jacek T,Katarzyna P,Agnieszka K,et al.The Role of IL-17 and Th17Lymphocytes in Autoimmune Diseases.Archivum Immunologiae etTherapiae Experimentalis,2015,63:435-449
[2]Kaser A,Zeissig S,Blumberg R.Inflammatory bowel disease.AnnuRev Immunol,2010,28:573-621
[3]戴萌,金雷,徐维田,等.TGF-β1中和抗体对TNBS慢性结肠炎动物模型纤维化的影响.世界华人消化杂志,2017,25(9):783-791
[4]张声生,沈洪,郑凯,等.溃疡性结肠炎中医诊疗专家共识意见(2017).中华中医药杂志,2017,32(8):3585-3589
[5]刘国山,施丽婕.溃疡性结肠炎在中医药领域中的文本挖掘.中医药学报,2017,45(4):40-43
[6]王爽,潘丹烨,甘爱萍.中医治疗溃疡性结肠炎研究概况.实用中医药杂志,2017,33(10):1225-1227
[7]Alex P,Zachos N C,Nguyen T,et al.Distinct cytokine patternsidentified from multiplex profiles of murine DSS and TNBS-induced colitis.Inflamm Bowel Dis,2009,15:341-352
[8]Rachmilewitz D,Karmeli F,Takabayashi K,et al.ImmunostimulatoryDNA ameliorates experimental and spontaneous murine colitis.Gastroenterology,2002,122:1428-1441
[9]Sujin Kang,Tatsusada Okuno,Noriko Takegahara,et al.IntestinalEpithelial Cell-derived Semaphorin 7A Negatively regulatesdevelopment of colitis viaαvβ1 integrin.The Journal ofImmunology,2012,188:1108-1116
[10]G Dothel,V Vasina,G Barbara,et al.Animal models of chemicallyinduced inflammation:Predictivity and ethical issues.Pharmacology&Therapeutics,2013,139:71-86
[11]徐连登,张宇霞,郑献敏.四神丸合四逆散治疗溃疡性结肠炎42例临床观察.吉林中医药,2012,32(5):483-484
[12]王玉珏.加味香连丸治疗溃疡性结肠炎63例.云南中医中药杂志,2010,31(4):86-87
[13]程虹,蒋巧俐,吴东方.青藤碱对TNBS诱导的慢性小鼠结肠炎的治疗作用.中国药师,2017,20(3):449-452
[14]陈东,王建民,李明,等.肠愈灌肠方对溃疡性结肠炎大鼠炎症相关因子及DOR、β-arrestin1、Bcl-2表达影响.中医药临床杂志,2017,29(1):90-94
[15]徐洋洋,蔡皓,段煜,等.白术芍药散治疗溃疡性结肠炎研究进展.中国中药杂志,2017,42(5):856-862
[16]Janek V,Kiyokazu K,Manjit B,et al.Reciprocal regulation ofsubstance P and IL-12/IL-23 and the associated cytokines, IFNγ/IL-17:A perspective on the relevance of this interaction to multipleSclerosis.Journal of Neuroimmune Pharmacology,2015,10:457-467
[17]P J Morrison,S J Ballantyne,M C Kullberg.Interleukin-23 and Thelper 17-type responses in intestinal inflammation:From cytokinesto T-cell plasticity.Immunology,2011,133:397-408
[18]Jacek T,Katarzyna P,Agnieszka K,et al.The Role of IL-17 and Th17Lymphocytes in Autoimmune Diseases.Archivum Immunologiae etTherapiae Experimentalis,2015,63:435-449