补体激活在流感病毒介导的肺部炎性损伤中的作用及眼镜蛇毒因子干预的实验研究  

Role of complement activation and CVF intervention in lung inflammatory injury induced by influenza virus

作　　者：赵希捷 周丽娟[1,3] 李桂萍[3] 史云[1] 郭瑞霞[4] 杨佐军[2] 贾雷立[1] 刘雪林[1] 宋宏彬[1] 张传福[1] ZHAO Xi-jie ZHOU Li-juan LI Gui-ping SHI Yun GUO Rui-xia YANG Zuo-jun JIA Lei-li LIU Xue-lin SONG Hong-bin ZHANG Chuan-fu(Institute of Disease Prevention and Control, Academy of Military Medical Sciences, Beijing 100071, China Institute of Animal Science and Technology, Beijing Agricuhural College, Beijing 102206, China Huaibei Normal University, Huaibei, Anhui 235000, China Shanxi Medical University, Taiyuan 030001, China)

机构地区：[1]军事医学科学院疾病预防控制所,北京100071 [2]北京农学院动物科学技术学院,北京102206 [3]淮北师范大学,安徽淮北235000 [4]山西医科大学,太原030001

出　　处：《军事医学》2016年第12期969-973,共5页Military Medical Sciences

基　　金：国家高技术研究发展计划资助项目(2014AA020516);吉林省人兽共患病预防与控制重点实验室-省部共建国家重点实验室培育基地开放课题基金资助项目(2012ZPC);国家自然科学基金资助项目(81000723)

摘　　要：目的揭示流感病毒介导的小鼠肺部炎性损伤机制,为研发治疗病毒性肺炎的有效药物提供理论和技术依据。方法建立流感PR8感染小鼠动物模型,利用实时荧光定量PCR、ELISA、病理切片等方法检测小鼠肺部炎症因子、补体分子及病理变化;按照50μg/(kg·24 h)的剂量腹腔注射眼镜蛇毒因子(CVF),监测小鼠体质量、存活率、炎症因子等变化。结果与对照组相比,PR8流感模型组小鼠肺组织中补体调节分子Crry、CD59表达显著下降(P<0.01),补体分子C9和补体成分受体C3aR、C5aR表达显著升高(P<0.01),血清中促炎因子TNF-α、IL-6、IFN-γ高表达,抗炎因子IL-2低表达(P<0.05);经CVF药物干预后,小鼠体质量下降缓慢,存活率升高,肺指数降低(P<0.05),抗炎因子IL-2表达明显升高(P<0.05),促炎因子IL-6、TNF-α、INF-γ表达显著下降。结论补体激活参与了流感病毒介导的肺部炎性损伤;通过CVF干预,抑制了补体激活,可提高感染小鼠存活率,降低肺指数,延缓病程。Objective To investigate the mechanism of pulmonary inflammation induced by influenza virus, and provide reference for the development of effective drugs for viral pneumonia. Methods An influenza PR8 infection mouse model was established. The levels of inflammatory cytokines and complement molecules were determined using RT-PCR and ELISA. The pathological changes were examined using biopsy. The complement inhibitor cobra venom factor （CVF） was injected intraperitoneally at a dose of 50 μg/（ kg · 24 h） , and then body mass. The survival rate and inflammatory factors were examined. Results Compared with the control group, the expressions of complement regulatory molecule Crry and CD59 were significantly decreased （P 〈0.01 ）, while those of complement C9 and complement receptor C3aR and CSaR were significantly increased in the lungs of influenza model mice （P 〈 0.01 ）. Pro-inflammatory cytokines TNF-α, IL-6 and IFN-γ were highly expressed, but anti-inflammatory eytokine IL-2 was lowly expressed in serum. Treatment with CVF caused a sight body mass loss, a survival rate increase and a lung index decrease （ P 〈 0. 05 ）. Moreover, an IL-2 expression increase and a decrease of IL45, TNF -α and INF-γ expression were observed in CVF treatment mice （P 〈0.05 ）. Conclusion Inhibition of complement activation can increase the survival rate of mice with influenza pneumonia and decrease pulmonary indexes, thus delaying the pathogenesis of PRS.

关 键 词：流感病毒 肺炎 补体 眼镜蛇毒因子 

分 类 号：R511.7[医药卫生—内科学] R563[医药卫生—临床医学]