轮状病毒致乳鼠肠道外感染Th1/Th2细胞因子变化的研究

Study on the change of Th1/Th2 cytokine after extraintestinal rotavirus infection in suckling mice

目的通过复制轮状病毒(RV)肠道外感染乳鼠的动物模型,检测接种后乳鼠体内Th1/Th2平衡改变,对RV肠道外感染后机体免疫状态进行初步研究。方法48只乳鼠随机均分为3组:肠道外组、肠道内组和正常对照组。肠道外组通过腹腔注射猴RVSA11株,肠道内组灌胃等量RV悬液,对照组无特殊处理。分别在接种后第4天、第8天处死乳鼠,收集标本,观察心、肝、肾、肺等脏器病理变化,用ELISA法检测血清中IL-10和IFN-γ的表达。结果光镜下肠道外组乳鼠肾、肝、肺和脾脏出现病理改变。感染后第4天,肠道内、外组乳鼠血清IFN-γ水平均高于正常组,到第8天明显下降,基本达到基线水平;IL-10在肠道外组第4天增高,到第8天小幅下降,但仍然高于正常组;而肠道内组IL-10无明显改变。结论RV肠道外感染早期呈现Th1-Th2混合反应,而后期则以IL-10的表达为主,T细胞向Th2型免疫应答方向偏离,Th1/Th2细胞因子失衡机制可能是RV肠道外感染的重要因素。

Objective To assess the distribution characteristics of Th2-type cytokine （interferon-γ, IFN-γ） and Th2-type cytokine （interleukin-10, IL-10） in the serum of ICR suckling mice inoculated by intraperitoneal injection with Simian Rotavirus SA11, so as to gain insight into the possible role of the systemic Th1/Th2 cell-mediated immune response in the pathogenesis of extraintestinal rotavirus infection. Method 48 ICR suckling mice were randomly divided into three groups ： extraintestinal groups inoculated by intraperitoneal injection with Simian Rotavirus SA11, intestinal groups inoculated by oral gavage with tales doses of rotavirus, and control groups with no special handling. At 4 and 8 days after infection, the pathological changes of extraintestinal tissue were examined under light microscopy and the levels of IFN-γ and IL-10 in the serum were measured with enzyme linked immunosorbent assay （ELISA）. Result Varying degrees of pathological changes were observed in the liver, kidneys, spleens and lungs in the extraintestinal group. 4 days after infection, die levels of IFN- γ began to increase in extraintestinal and intestinal groups, then decrease at the days 8 to the level of base line. IL-10 in extraintestinal group increased on day 4, then decreased on day 8, yet still increasing compared with the control group. In intestinal groups,the IL-10 had no significant change. Conclusion After extraintestinal rotavirus infection,the cell immune respone showed Th1-Th2 type immune response in the early stage. But in the late stage,IL-10 expression predominated and the cell immune respone switched to Th2 type immune response. Th1/Th2 imbalance in cytokines may be an important factor in extraintestinal rotavirus infection.