阻断补体C3a抑制ILC2功能对小鼠哮喘的影响研究  

Effect of Blocking Complement C3aInhibiting ILC2Function in Mice with Asthma

作　　者：钱振 辛培源 华瑞 李立宏 付国强 张海涛 QIAN Zhen;XIN Peiyuan;HUA Rui;LI Lihong;FU Guoqiang;ZHANG Haitao(Department of Emergency,Tangdu Hospital,Xi′an Shaanxi 710038,China)

机构地区：[1]空军军医大学第二附属医院(唐都医院)急诊科,陕西西安710038 [2]空军军医大学第二附属医院(唐都医院)呼吸科,陕西西安710038 [3]中国人民解放军93721部队医院

出　　处：《华南国防医学杂志》2022年第7期499-502,516,共5页Military Medical Journal of South China

基　　金：国家自然科学基金(82103537);陕西省重点研发计划(2016MSZD-S-2-6)。

摘　　要：目的研究C3a信号在哮喘发病中的作用。方法采用BALB/c小鼠建立卵清蛋白(ovalbumin,OVA)诱导的小鼠哮喘模型,腹腔给予C3a受体(C3a receptor,C3aR)拮抗剂后,检测肺组织功能和炎症相关指标的变化。结果模型组小鼠肺组织气道阻力显著升高,肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中有大量嗜酸性粒细胞浸润,肺组织匀浆中白细胞介素4(interleukin 4,IL-4)、IL-5和IL-13显著升高(P均<0.05),基质金属蛋白酶2(matrix metalloproteinase,MMP-2)和MMP-9在肺中表达明显升高(P均<0.05)。应用拮抗剂阻断C3aR信号后,小鼠肺功能显著好转,BALF中嗜酸性粒细胞浸润明显减少,同时肺组织中相关炎症指标显著下降(P均<0.05),肺组织中2型固有淋巴样细胞(type 2innate lymphoid cell,ILC2)的细胞因子分泌明显降低(P均<0.05)。结论补体C3a与哮喘的发病关系密切,且有可能是通过影响ILC2功能发挥作用。Objective To study the role of C3a signal in the pathogenesis of asthma.Methods A mice model of asthma induced by ovalbumin(OVA)was established by BALB/c mice.After intraperitoneal administration of C3a receptor(C3aR)antagonist,the changes of lung function and inflammation related protein were detected.Results In model group,the airway resistance of lung tissue was significantly increased,a large number of eosinophils were infiltrated in bronchoalveolar lavage fluid(BALF),and interleukine 4(IL-4),IL-5 and IL-13 were significantly increased in lung tissue homogenate(all P<0.05),the expression of matrix metalloproteinase(MMP-2)and MMP-9 were significantly increased in lung(all P<0.05).After the application of antagonist to block C3aR signal,the lung function of mice was significantly improved,the infiltration of eosinophils in BALF was significantly reduced,and the relevant inflammatory indexes in lung tissue were significantly decreased(all P<0.05).The cytokine secretion of type 2 innate lymphoid cell(ILC2)in lung tissue was significantly decreased(all P<0.05).Conclusion Complement C3a is closely related to the pathogenesis of asthma,and may play a role by affecting the function of ILC2 cells.

关 键 词：哮喘 C3A C3a受体 肺组织 2型固有淋巴样细胞 

分 类 号：R562.25[医药卫生—呼吸系统]