旋毛虫对不同肠炎模型小鼠脾脏淋巴细胞Th1/Th2水平的影响
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摘要
目的:研究旋毛虫(T.spiralis)对肠炎小鼠[三硝基苯磺酸(TNBS)或唑酮(OXZ)诱导]脾脏淋巴细胞中Th1/Th2水平的影响。方法:雌性BALB/c小鼠,随机分为50%乙醇对照组、TNBS(OXZ)诱导肠炎模型组、预先感染T.spiralis后诱导TNBS(OXZ)模型组,每组小鼠取材时保证6只以上。对各组小鼠脾脏淋巴细胞进行分离,采用流式细胞术观察TNBS(OXZ)诱导肠炎模型组和预先感染T.spiralis后诱导TNBS(OXZ)模型组。造模后3 d和7 d脾脏淋巴细胞中Th1/Th2水平的变化。结果:与模型组相比,预先感染T.spiralis后诱导TNBS肠炎第3天脾脏Th1/Th2比值未见明显下降(P>0.05),于第7天明显降低(P<0.05)。诱导OXZ肠炎模型后第3天及第7天小鼠脾脏Th1/Th2比值均明显低于T.spiralis干预组(P<0.05)。结论:针对TNBS肠炎模型,T.spiralis可能是通过诱导Th2及Tr1型免疫反应抑制模型小鼠过度的Th1型免疫而起到良好的干预作用。在T.spiralis对OXZ模型小鼠的干预性研究中,并无T.spiralis感染诱发的Th2型炎症反应加重同样以Th2升高为主的OXZ模型小鼠的病情。
Objective: To study the levels of Th1 and Th2 in spleen lymphocyte of TNBS and OXZ colitis without or with Trichinella spiralis( T. spiralis) infection. Methods: Female BALB/c mice were randomly divided into 3 groups: 50% Ethanol,TNBS or OXZ,T. spiralis+TNBS or OXZ( at least 6 in each group when mice were killed). The ratio of Th1/Th2 lymphocyte in spleen was detected by FCM with three color intracellular cytokine staining. Results: In spleen lymphocyte of TNBS colitic mice with prior nematode infection,the ratio of Th1/Th2 were not significantly different compared with that seen in colitic mice without prior nematode infection on day 3 post-induction of colitis( P>0. 05),the ratio of Th1/Th2 was significantly lower than which on day 7 post-induction of colitis( P<0. 05). In spleen lymphocyte of OXZ colitic mice with prior nematode infection on days 3 and 7 post-induction of colitis,the ratio of Th1/Th2 was significantly higher than that seen in colitic mice without prior nematode infection( P < 0. 05). Conclusion: Infection of mice with T. spiralis distracts the mucosal immune system response from a Th1 response toward a protective Th2 response and up-regulate Tr1-cytokines with an attendant reduction in the severity of colonic damage and balance of Th1/Th2. Prior T. spiralis infection doesn't reduce the severity of OXZ-induced colitis,but without aggravating colitis.
Objective: To study the levels of Th1 and Th2 in spleen lymphocyte of TNBS and OXZ colitis without or with Trichinella spiralis( T. spiralis) infection. Methods: Female BALB/c mice were randomly divided into 3 groups: 50% Ethanol,TNBS or OXZ,T. spiralis+TNBS or OXZ( at least 6 in each group when mice were killed). The ratio of Th1/Th2 lymphocyte in spleen was detected by FCM with three color intracellular cytokine staining. Results: In spleen lymphocyte of TNBS colitic mice with prior nematode infection,the ratio of Th1/Th2 were not significantly different compared with that seen in colitic mice without prior nematode infection on day 3 post-induction of colitis( P>0. 05),the ratio of Th1/Th2 was significantly lower than which on day 7 post-induction of colitis( P<0. 05). In spleen lymphocyte of OXZ colitic mice with prior nematode infection on days 3 and 7 post-induction of colitis,the ratio of Th1/Th2 was significantly higher than that seen in colitic mice without prior nematode infection( P < 0. 05). Conclusion: Infection of mice with T. spiralis distracts the mucosal immune system response from a Th1 response toward a protective Th2 response and up-regulate Tr1-cytokines with an attendant reduction in the severity of colonic damage and balance of Th1/Th2. Prior T. spiralis infection doesn't reduce the severity of OXZ-induced colitis,but without aggravating colitis.
引文
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[2]Blumberg RS,Strober W.Prospects for research in inflammatory bowel disease[J].JAMA,2001,285(5):643-647.
[3]Braegger CP,Macdonald TT.Immune mechanisms in chronic inflammatory bowel disease[J].Ann Allergy,1994,72(2):135-141.
[4]Li X,Song P,Li J,et al.The disease burden and clinical characteristics of inflammatory bowel disease in the chinese population:a systematic review and meta-analysis[J].Int J Environ Res Public Health,2017,14(3):pii:E238.
[5]Elliott DE,Urban JF JR,Argo CK,et al.Does failure to acquire hel minth parasites predispose to Crohn's disease?[J].FASEB J,2000,14(12):1848-1855.
[6]Varyani F,Fleming JO,Maizels RM.Helminths in the gastrointestinal tract as modulators of immunity and pathology[J].Am JPhysiol Gastrointest Liver Physiol,2017,312(6):G537-G549.
[7]赵颖,杨世忠,邹洪斌,等.旋毛虫对三硝基苯磺酸诱导的实验性小鼠肠炎模型的干预研究[J].中华微生物学和免疫学杂志,2007,27(6):509-512.Zhao Y,Yang SZ,Zou HP,et al.Trichinella spiralis infection protects mice from TNBS-induced colitis[J].Chin J Microbiol Immunol,2007,27(6):509-512.
[8]Stallmach A,Marth T,Weiss B,et al.An interleukin 12 p40-Ig G2b fusion protein abrogates T cell mediated inflammation:anti-inflammatory activity in Crohn's disease and experimental colitis in vivo[J].Gut,2004,53:339-345.
[9]Heller F,Fuss IJ,Nieuwenhuis EE,et al.Oxazolone colitis,a Th2colitis model resembling ulcerative colitis,is mediated by IL-13-producing NK-T cells[J].Immunity,2002,17(5):629-638.
[10]Else KJ,Finkelman FD.Intestinal nematode parasites,cytokines and effector mechanisms[J].Int J Parasitol,1998,28(8):1145-1158.
[11]Cvetkovic J,Sofronic-Milosavljevic L,Ilic N,et al.Immunomodulatory potential of particular Trichinella spiralis muscle larvae excretory-secretory components[J].Int J Parasitol,2016,46(13-14):833-842.
[12]王开,裴志花,胡桂学,等.肠炎动物模型的研究进展[J].中国免疫学杂志,2015,31(5):704-706.Wang K,Pei ZH,Hu GX,et al.Advances in animal models of enteritis[J].Chin J Immunol,2015,31(5):704-706.
[13]Elson CO,Beagley KW,Sharmanov AT,et al.Hapten-induced model of murine inflammatory bowel disease.Mucosal immune responses and protection by tolerance[J].J Immunol,1996,157(5):2174-2185.
[14]Boirivant M,Fuss IJ,Chu A,et al.Oxazolone colitis:a murine model of t helper cell type 2 colitis treatable with antibodies to interleukin 4[J].J Exp Med,1998,188(10):1929-1939.
[15]Murphy KM,Reiner SL.The lineage decisions of helper T cells[J].Nat Rev Immunol,2002,2(12):933-944.
[16]赵颖,赵英,窦海川,等.旋毛虫对噁唑酮诱导的实验性小鼠肠炎模型的干预研究[J].中华微生物学和免疫学杂志,2016,36(1):34-41.Zhao Y,Zhao Y,Dou HC,et al.Effects of Trichinella spiralis infection on a murine model of OXZ-induced colitis[J].Chin J Microbiol Immunol,2016,36(1):34-41.
[17]Tilg H,van Montfrans C,van den Ende A,et al.Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma[J].Gut,2002,50(2):191-195.