旋毛虫对三硝基苯磺酸和噁唑酮诱导肠炎小鼠结肠中Th1/Th2类细胞因子表达的影响

目的 研究旋毛虫(T. spiralis)对三硝基苯磺酸(TNBS)和噁唑酮(OXZ)诱导的实验性肠炎小鼠结肠中Th1/Th2类细胞因子表达的影响.方法 雌性BALB/c小鼠,随机分为50%乙醇对照组、T. spiralis应用组、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).对各组小鼠肠黏膜固有层单个核细胞(LPMC)进行分离培养,采用ELISA方法观察感染T.spiralis和未感染T.spiralis小鼠于TNBS或OXZ诱导肠炎后3 d和7 d结肠中Th1/Th2类细胞因子蛋白的表达变化,包括IFN-γ、IL-12、IL-4、IL-10的表达量分析.结果 预先感染T. spiralis后诱导TNBS模型组小鼠在造模后3 d及7 d肠黏膜LPMC产生IFN-γ的水平均低于模型组(P＜0.05),而IL-4、IL-10的表达高于模型组(P＜0.05).预先感染T. spiralis后诱导TNBS模型组小鼠在造模后3 d肠黏膜LPMC产生IL-12的水平低于模型组(P＜0.05),第7天与模型组相比未见明显差异(P＞0.05).预先感染T. spiralis后诱导OXZ模型组小鼠在造模后3 d及7 d肠黏膜LPMC产生IFN-γ、IL-4及IL-10的水平均高于单纯造模组(P＜0.05).结论 T. spiralis对TNBS诱导的肠炎模型小鼠肠道局部免疫作用机制可能是通过诱导Th2型免疫反应及Tr1型细胞因子而抑制结肠炎小鼠Th1型过度免疫应答而实现的.在T.spiralis对OXZ模型小鼠的干预性研究中,没有按理论所设想的感染T.spiralis所产生的Th2型免疫反应会对OXZ诱导的Th2型炎症反应起叠加作用而加重病情.这提示我们,需要进一步探讨T.spiralis对拥有Th2型免疫应答的OXZ模型的具体作用机制.

Levels of Th1/Th2 type cytokines in TNBS and OXZ colitis without or with Trichinella spiralis infection

Objective To study the levels of Th1 and Th2 type cytokines in 3-nitrobenzene sulfonate(TNBS) and oxazolone(OXZ) colitis without or with Trichinella spiralis( T. spiralis) infection. Methods Female BALB/c mice were randomly divided into 4 groups: 50% Ethanol, T. spiralis only, TNBS or OXZ,T. spiralis +TNBS or OXZ(at least 6 in each group when mice were killed). The levels of IFN-γ, IL-12,IL-4, IL-10 in colon in mice with colitis induced by TNBS or OXZ without or with T. spiralis infection 3 d and 7 d post-induction were assessed using ELISA method. Results Colonic protein levels of IFN-γand IL-12 were significantly increased 3 d and 7 d after intra-colonic injection of TNBS( P ＜0.05 ). Concurrent infection with T. spiralis prevented this rise in IFN-γand IL-12 secretion and tended to induce a rise in colonic IL-4 and IL-10 content(P ＜0. 05). The levels of IFN-γ, IL-4 and IL-10 protein in colitic mice colon with prior nematode infection on days 3 and 7 post-induction of colitis were significantly higher than that seen in colitic mice without prior nematode infection ( P ＜ 0.05 ). Conclusion T. spiralis infection significantly attenuates TNBS-induced colitis in mice. The local immunologic mechanism is that T. spiralis can down-regulate strongly Th1-type immune response of colitis and up-regulate Th2 response, Tr1-cytokines. According to the change of Th1/Th2 cytokines, prior T. spiralis infection doesn't reduce the severity of OXZ-induced colitis, but without aggravating colitis. The exactly immunologic mechanism deserve to be explored deeply.