摘要
目的探究甲型流行性感冒(流感)病毒感染后粒细胞-巨噬细胞集落刺激因子(GM-CSF)对M1样气道单核细胞巨噬细胞极化的影响。方法选取雄性NC/Nga小鼠(8周龄)60只,随机分成甲型流感病毒感染组(对照组,n=30)和GM-CSF过表达组(过表达组,n=30)。评估2组甲型流感感染的发病率和病死率,测定诱导GM-CSF的过表达及纯化对小鼠呼吸力学参数和支气管肺泡灌洗蛋白质(BAL)的影响;观察巨噬细胞的单核细胞分离、分化和极化;利用PCR法测定M1样气道单核/巨噬细胞极化标记基因的表达。结果过表达组的发病率低于对照组(P<0.05);过表达组的病死率低于对照组(P<0.05)。对照组的呼吸力学参数<过表达组(P<0.05);对照组的压力容积(PV)曲线的曲率<过表达组(P<0.05);对照组呼吸系统总阻力和组织或外围气道阻力>过表达组(P<0.05)。过表达组细胞因子CCL17、CXCL9和MMP12的BAL蛋白表达水平高于对照组(P<0.05)。对照组的组织中CD11b^+标记气道单核细胞/巨噬细胞极化高于过表达组(P<0.05)。提示正常组织中巨噬细胞以M2型为主,减少炎症反应。对照组中巨噬细胞M1样mRNA水平较高,其中TNF-α、MCP-1、IL-6 mRNA表达水平高于过表达组(P<0.05)。结论GM-CSF过表达改善了甲型流感病毒感染对肺力学的影响,抑制M1样气道单核细胞/巨噬细胞极化则提示极化以M2样为主,减少炎症反应。
Objective To investigate the effect of granulocyte-macrophage colony-stimulating factor(GM-CSF)on M1-like airway monocyte/macrophage polarization after influenza A virus infection.Methods Sixty male NC/Nga mice(8 weeks old)were randomly divided into two groups:influenza A virus infection group(control group,n=30)and GM-CSF overexpression group(overexpression group,n=30).The morbidity and mortality associated with influenza A virus infection were evaluated,and monocyte separation,differentiation and polarization of macrophages were observed.The effects of GM-CSF overexpression and purification on mechanical lung parameters and bronchoalveolar lavage proteins were measured.The expression of M1-like monocyte/macrophage polarization marker genes was detected by PCR.Results Compared with overexpression group,the morbidity,mortality,total respiratory resistance,tissue or peripheral airway resistance,expression of TNF-α,MCP-1 and IL-6 mRNA and polarization of CD11b^+-labeled airway monocytes/macrophages increased,but mechanical lung parameters and PV curve curvature decreased in control group(P<0.05).BAL protein expression levels of CCL17,CXCL9 and mmp12 in overexpression group were higher than those in control group(P<0.05).Conclusion GM-CSF overexpression can improve the effect of influenza A virus infection on lung mechanics and reduce inflammatory response.The inhibition of M1-like airway monocyte/macrophage polarization suggests that M2-like polarization is the main polarization.
作者
柯文玲
赵艳雪
KE Wen-ling;ZHAO Yan-xue(Department of Paediatrics,Shiyan Maternal and Child Health Hospital,Shiyan 442000,China)
出处
《南昌大学学报（医学版）》
CAS
2020年第4期23-27,31,共6页
Journal of Nanchang University：Medical Sciences
