轮状病毒感染全身扩散诱发因素的初探

Factors triggering extraintestinal infection of rotavirus

目的探讨免疫低下、肠道混合感染因素在诱发轮状病毒(RV)肠道外扩散中的作用,为研究肠道病毒肠道外扩散的机制,为临床的防治提供参考。方法健康昆明小鼠腹腔注射环磷酰氨制作免疫低下小鼠模型,分别经灌胃和腹腔两种途径接种RV;健康昆明小鼠相继灌胃接种产毒性大肠杆菌和RV,制作肠道混合感染小鼠模型;猝死小鼠,光镜下观察病理变化;各脏器原位杂交,原位PCR检测RV;初步调查RV腹泻合并轮状病毒血症患儿健康状况,检测TNFα、IL-2及锌、铁、铜、铅、钙、锰、镁7种微量元素水平。结果光镜下:免疫低下组心、肝、肾,混合感染组肝、肾组织有病理改变;原位杂交:免疫低下腹腔注射RV组、肠道混合感染组肾小管均呈阳性。原位PCR:肠道混合感染组肝、肾,免疫低下腹腔注射组心、肝、肾、胰呈阳性;轮状病毒血症患儿多数存在免疫与营养方面的异常。结论免疫低下、肠道混合感染、营养素不足可能是诱发和/或加重RV肠道外扩散和感染的重要原因之一。

Objective To investigate the role of immunodeficiency and intestinal mixed infection on inducing extraintestinal dissemination of rotavirus （RV）. Methods Immtmodeficiency was induced in healthy Kunming mice by introperitoneal injection of cyclophosphamide, and RV was administered either orally or via intraperitoneal injection. In another group, toxigenic E.coli and human RV were given sequentially by intragastric administration to induce mixed infection. Three days later the organs of the mice were taken for pathological examination, and RV was detected by in situ PCR and hybridization. In children with or without viremia of rotavirus, blood tests for levels of tumor necrosis factor α （TNF-α）, interleukin-2 （IL-2） and 7 trace elements （zinc, iron, copper, lead, calcium, manganese, and magnesium） were performed. Results In immunodeficient mice, pathological changes were found in the small intestinal villus, gastric lamina propria and the cardiac cells of mice taking RV orally, and the mice with intraperitoneal RV injection showed additional liver and kidney pathologies. In mice with mixed infections, pathological changes occurred in the intestines, livers and kidneys. In situ hybridization detected RV in the intestinal villius of immunodeficient mice with oral RV administration, and in the intestinal villus and kidneys of the mice with mixed infections. In situ PCR revealed the presence of RV in the intestinal villus, intestinal gland cells, epithelial cells of the proximal convoluted tubules and collecting tubes in the kidneys of immunodeficient mice taking RV orally, in the intestinal villus, kidneys, livers, hearts and pancreases of those with RV injection, and in the intestines, kidneys, and livers of the mice with mixed infection. Children with rotavirus viremia had TNF-α level in comparison with those free of rotavirus viremia, and the majority of the former children showed disorder in trace elements. Conclusion Immunodeficiency, mixed infection and malnutrition can be important factors contributing to or exacerbating RV infection and extraintestinal RV dissemination.