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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 reveal the mechanism of influenza virus-induced lung inflammation in mice and to provide theoretical and technical basis for the development of effective drugs for the treatment of viral pneumonia. Methods Animal models of influenza virus infection in PR8 were established. The lung inflammatory cytokines, complement molecules and pathological changes were detected by real-time fluorescence quantitative PCR, ELISA and pathological sections. The mice were injected intraperitoneally with 50μg / (kg · 24 h) Toxicokine (CVF), monitoring body weight, survival rate, inflammatory factors and other changes. Results Compared with the control group, the expressions of Cr39 and CD59 in the lung tissue of PR8 influenza model group were significantly decreased (P <0.01), and the expressions of C9 and C3aR and C5aR were significantly increased (P <0.01) ), High expression of proinflammatory cytokines TNF-α, IL-6 and IFN-γ in sera and low expression of anti-inflammatory cytokines IL-2 (P <0.05). After CVF treatment, the body weight of mice decreased slowly and the survival rate (P <0.05). The expression of anti-inflammatory cytokines IL-2 was significantly increased (P <0.05) and the expressions of proinflammatory cytokines IL-6, TNF-α and INF-γ were significantly decreased. Conclusion Complement activation is involved in influenza virus-mediated inflammatory injury of the lungs. By intervention of CVF, complement activation can be inhibited, which can increase the survival rate of infected mice, decrease the pulmonary index and delay the course of disease.