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目的 探讨巨噬细胞SIRT1-NF-κB信号转导途径在流感病毒感染小鼠体内的调节机制.方法 用流感病毒血凝素蛋白(HA)和核衣壳蛋白(NP)蛋白免疫小鼠,取小鼠腹腔巨噬细胞,采用ELISA法检测细胞培养上清中促炎症因子IL-1β、IL-6、IL-18和肿瘤坏死因子α(TNF-α)的含量;采用实时荧光定量PCR检测细胞内沉默信息调节因子1(SIRT1)、NF-κB、IL-1β、IL-6、IL-18以及TNF-α的基因表达.结果 两组蛋白初次免疫后巨噬细胞分泌的各因子及其mRNA表达水平均无明显变化.二次免疫后,HA蛋白组仅TNF-α、IL-6蛋白表达水平增加,与对照组比较差异有统计学意义,NP蛋白组IL-1β、IL-6、IL-18和TNF-α蛋白表达水平均增加,与对照组比较差异均有统计学意义;而两组蛋白刺激后巨噬细胞TNF-α、IL-6 mRNA均表达上调,SIRT1 mRNA均表达下调,与对照组比较差异有统计学意义.结论 流感病毒可能通过所表达的HA、NP等蛋白影响SIRT1的活性,从而解除SIRT1对NF-κB的抑制作用,激活NF-κB信号通路调节的炎症反应或免疫应答.“,”Objective To explore the regulatory mechanism of SIRT1-NF-κB signal transduction pathway against influenza virus infection in mice.Methods The hemagglutinin (HA) and nucleoprotein (NP) of influenza virus were used to immunize mice.Macrophages were collected 10 days after the first and second immunization.The mRNA expression levels of SIRT1 、NF-κB、IL-1 β,IL-6,IL-18 and TNF-α genes were analyzed by real-time quantitative PCR.The protein expression levels of IL-1 β,IL-6,IL-18,TNF-αwere detected by ELISA.Results No significant difference was found with the expression levels of mRNA and protein of all cytokines after the first immunization.After the second immunization,the protein expression levels of TNF-α and IL-6 were significantly increased in HA group,while the protein expression levels of IL-1 β,IL-6,IL-18 and TNF-α were all significantly increased in NP group.The mRNA expression levels of TNF-α and IL-6 were significantly increased in both groups,and the level of SIRT1 was significantly decreased.Conclusions The HA and NP of influenza virus may affect the activity of SIRT1,and its inhibitory effect on NF-κB was released,then the inflammatory or immune response mediated by NF-κB signal pathway was activated.