猴艾滋病模型炎症因子表达

【作者】 刘翠华； 吴胜男； 何金洋；

【机构】 广州中医药大学热带医学研究所；

【摘要】 目的:观察SIVmac251感染中国恒河猴前后炎症相关细胞因子的表达变化。方法:16只中国恒河猴感染SIVmac251,在感染前1天,感染2、4、6、8、10周分别采集外周静脉血,于感染前1天及感染10周采集浅表淋巴结和直肠组织。用染料法荧光定量PCR检测外周血PBMC和浅表淋巴结组织炎症及免疫活化相关mRNA水平,用Elisa及流式细胞仪检测血浆炎症及免疫活化相关蛋白;用HE染色和免疫组化检测浅表淋巴结组织和直肠黏膜组织病理改变情况和炎症相关细胞因子表达。结果:SIVmac251感染中国恒河猴后,其外周血PBMC、浅表淋巴结组织中IL-6、CD38、HLA-DR、IL-1β、IFN-a4、MyD88、IL-33、TLR2、TLR7、HMG-B1、IL-18mRNA显著升高;CD4~+CD38~+HLA-DR~+细胞占CD4+T细胞百分比在SIV感染后显著上升;血浆IL-6、IL-1β、IL-18、IFN-γ、D-二聚体水平均显著升高;SIV感染后恒河猴浅表淋巴结出现了显著的病理改变,表现为纤维化、淋巴滤泡增生、耗竭等现象;肠道黏膜HE染色则显示明显炎症。免疫组化染色结果显示,浅表淋巴结组织和直肠黏膜组织IL-1β、IL-18及HLA-DR表达均明显升高。结论:SIV感染引发了显著的炎症反应,这种炎症反应的特点是与免疫活化程度紧密相关。更多还原

【Abstract】 Objectives:Observation of the dynamic changes of inflammation related cytokines before and after the SIV infection.Methods:16 rhesus monkeys were infected with SIVmac251.The peripheral blood was drew at the time points of 1 day before SIV infection and 2 weeks,4 weeks,6 weeks,8 weeks,10 weeks after SIV infection respectively.The Superficial lymph nodes tissues and Rectal mucosa tissues were collected 1 day before SIV infection and 10 weeks after SIV infection.The inflammation and immune activation related cytokines mRNA were tested with Fluorescent quantitative PCR.The proteins of the inflammation and immune activation related cytokines were tested with Elisa and flow cytometry.The phthological changes and the inflammation and immune activation related cytokines expression in the Superficial lymph nodes tissue and Rectal mucosa tissue were tested with HE staining and Immunohistochemical staining.Results:After SIV infection,the mRNA of IL-6,CD38,HLA-DR,IL-1β,IFN-a4,MyD88,IL-33,TLR2,TLR7,HMG-B1,IL-18 in the PBMC and Superficial lymph nodes tissues were significantly increased.The ratio of CD4~+CD38~+HLA-DR~+ cells were significantly up-regulated relative to the CD4+T cells.The IL-6、IL-1β、IL-18、IFN-γ、D-dimer levels were markedly up-regulated.The pathological changes in the Superficial lymph nodes tissues mainly presented as fibrosis,lymph foilicie hyperplasia and exhaust.The rectal mucosa tissues mainly presented as inflammation.The Immunohistochemical staining showed that the IL-1β、IL-18 and HLA-DR expression in both the Superficial lymph nodes tissues and Rectal mucosa tissues were significantly up-regulated.Conclusion:SIV infection can induce significant inflammation,which is closely related with immune activation.更多还原