呼吸道合胞病毒增加小鼠肺组织的高迁移率族蛋白B1的表达和释放

Respiratory syncytial virus increases the expression and release of high mobility group Box-1 protein in the lung tissue of mice

探讨呼吸道合胞病毒(RSV)感染小鼠模型肺组织高迁移率族蛋白B1(HMGB1)的表达和释放。方法18只Balb/C小鼠,随机分成3组,分别为磷酸盐缓冲液(PBS)对照组、RSV组、RSV+利巴韦林治疗组;RSV感染小鼠7d后处理:支气管肺泡灌洗液(BALF)作细胞分类计数,酶联免疫吸附试验(ELISA)测定BALF上清中白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)及HMGB1含量,左肺行苏木精-伊红(HE)染色,蛋白免疫印迹方法检测右肺组织HMGB1表达。结果1、RSV感染诱导了小鼠肺组织TH1型反应:BALF中的IFN-γ含量增加,IL-4含量减低。与对照组比较,RSV组BALF中细胞总数、中性粒细胞、巨噬细胞均显著增加(P<0.05),RSV+利巴韦林治疗组上述细胞数显著减低(P<0.05)。HE染色:RSV组可见黏膜下及管壁周围中性粒细胞,淋巴细胞等炎症细胞浸润。2、BALF中HMGB1含量变化:与对照组比较,RSV组显著升高(P<0.05)、利巴韦林治疗组显著降低(与RSV组比较,P<0.05)。3、肺组织HMGB1的表达情况:与对照组比较,RSV组明显升高(P<0.05)、治疗组无显著降低(与RSV组比较,P>0.05)。结论HMGB1在RSV感染小鼠的肺组织中表达和释放明显增加,提示其可能参与了RSV感染相关肺疾病的发生发展。

Objective To investigate the expression and release of high mobility group Box-1 protein （HMGB1） in the lung tissue of mice with respiratory syncytial virus （RSV） infection.Methods Eighteen mice were randomized into PBS control group,RSV group and RSV/ribavirin group.Seven days after RSV infection in the mice in the latter two groups,the bronchoalveolar lavage fluid （BALF） was collected for cell counting and classification,and the levels of IL-4,IFN-γ and HMGB1 in the supernatants of the BALF were detected.The left lungs of the mice were harvested for pathological examination with HE staining,and the right lungs were taken for detecting the expression of HMGB1 by Western blotting.Results RSV induced a TH1 inflammation in the lung tissue as shown by significantly increased IFN-γ and decreased IL-4 levels in the BALF.The total BALF cells,neutrophils and macrophages in the RSV group were significantly higher than those in the control group （P0.05）,and the cell counts were significantly decreased by ribavirin treatment （P0.05）.HE staining showed neutrophil and lymphocyte infiltration in the lumen and submucous layer of the airway in RSV group.The level of HMGB1 in the BALF significantly increased in the RSV group as compared with that in the control group （P0.05）,but was lowered by ribavirin treatment （P0.05）.The expression of the HMGB1 in the lung tissue significantly increased in the RSV group in comparison with that in the control group （P0.05）,and was not significantly decreased by ribavirin treatment （P0.05）.Conclusion The increased expression and release of HMGB1 in the lung tissue of mice with RSV infection is probably involved in the development of RSV infection-related lung diseases.