摘要
目的:观察过敏性哮喘加速小鼠动脉粥样硬化(AS)的发生和发展是否与Th2细胞及白细胞介素4(IL-4)有关,以及免疫球蛋白E(IgE)-Fc ε受体I(FcεRI)交联激活巨噬细胞途径在其中发挥的作用。方法:取6周龄的ApoE^(-/-)小鼠,以卵清蛋白致敏和激发建立过敏性哮喘模型,并分为对照组、哮喘安慰剂组和哮喘IL-4单克隆抗体干预组,分别干预8周,干预结束后处死小鼠,油红O染色检测主动脉根部斑块面积,流式细胞术检测脾脏Th2细胞比例,real-time PCR检测IL-4、IL-6、单核细胞趋化蛋白1(MCP1)和巨噬细胞炎症蛋白1α(MIP1α)的mRNA表达水平,ELISA法检测血清IL-4和IgE的含量。结果:与对照组相比,过敏性哮喘ApoE^(-/-)小鼠主动脉根部AS病变显著加重,并伴有体内Th2细胞和IL-4水平的增高,同时斑块处IgE和FcεRIα的表达显著增高,MCP-1、MIP-1α和IL-6的mRNA表达也显著增加;IL-4单克隆抗体干预8周后,主动脉根部AS病变缓解的同时,增高的IgE和FcεRIα表达被显著抑制,巨噬细胞相关炎性因子的表达水平也显著降低。结论:过敏性哮喘显著加速ApoE^(-/-)小鼠AS病变进展,此作用与体内Th2细胞和IL-4水平增加,以及IgE-FcεRI交联激活巨噬细胞途径有关。
AIM:To investigate whether allergic asthma accelerates the development of atherosclerosis in mice related to Th2 cells and interleukin-4(IL-4),and the roles of activation of macrophages by immunoglobulin E(IgE)-Fcεreceptor I(FcεRI)crosslink during the process.METHODS:Six-week-old ApoE-/-mice were sensitized and challenged by ovalbumin to establish the allergic asthma model,and then assigned to 3 groups:control group,asthmatic placebo group and asthmatic IL-4 monoclonal antibody(mAb)intervention group(intervention for 8 weeks).The lesion area was measured by oil red O staining.The percentages of Th2 cells in the splenocytes of the mice were analyzed by flow cytometry.The mRNA expression of IL-4 and the macrophage-related inflammatory factors,monocyte chemotactic protein 1(MCP-1),macrophage inflammatory protein-1α(MIP-1α)and IL-6,in the spleen was detected by real-time PCR.Local IgE and FcεRIαexpression in the plaque was evaluated by immunofluorescence/immunohistochemical staining,and the circulating IL-4 and IgE were measured by ELISA.RESULTS:Accompanied by aggravated atherogenesis in asthmatic ApoE-/-mice,the proportion of Th2 cells and IL-4 mRNA in the spleen,IgE and FcεRIαexpression in the aortic root,and the mRNA expression of MCP-1,MIP-1αand IL-6 were markedly increased.After 8-week treatment with IL-4 mAb,the lesion area in the aortic root of asthmatic ApoE-/-mice was markedly decreased,the elevated IgE and FcεRIαexpression was significantly decreased,and the mRNA expression of macrophage-related inflammatory factors was also decreased.CONCLUSION:Allergic asthma accelerates the atherosclerosis in ApoE-/-mice,which is associated with the increased Th2 cells and IL-4,and the activation of macrophages by IgE-FcεRI crosslink.
作者
郜珊珊
周娟
袁祖贻
王丽君
GAO Shan-shan;ZHOU Juan;YUAN Zu-yi;WANG Li-jun(Department of Cardiology,First Affiliated Hospital,Xi’an Jiaotong University,Xi’an 710061,China;Key Laboratory of Molecular Cardiology,Shaanxi Province,Xi’an Jiaotong University,Xi’an 710061,China;Key Laboratory of Environment and Genes Related to Diseases for Ministry of Education,Xi’an Jiaotong University,Xi’an 710061,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第9期1552-1557,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金青年基金资助项目(No.81500389
No.81700447)
