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作 者:陈伟苗 王梓宁 何爽 李蓉 CHEN Weimiao;WANG Zining;HE Shuang;LI Rong(Ocean University of China,Medical College,Qingdao 266000,China;Pharmacy Department,Qingdao Women and Children's Hospital,Qingdao 266034,China)
机构地区:[1]中国海洋大学医药学院,青岛266000 [2]青岛市妇女儿童医院药学部,青岛266034
出 处:《中国免疫学杂志》2025年第3期551-555,共5页Chinese Journal of Immunology
基 金:山东省医学会临床科研专项基金资助项目(YXH2022ZX01007)。
摘 要:目的:从免疫炎症和肺部菌群变化的角度探讨酪酸梭菌对哮喘的干预作用机制,为哮喘的防治提供新方案。方法:将小鼠随机分为酪酸梭菌组(CM)、哮喘模型组(Model)和正常对照组(Control),每组16只,模型组和酪酸梭菌组通过腹腔注射卵清蛋白(OVA)致敏及连续雾化激发(1%OVA溶液)建立哮喘小鼠模型,正常对照组用生理盐水代替OVA。酪酸梭菌组小鼠在雾化激发期间灌胃酪酸梭菌溶液,每只1×109 CFU/d。计数支气管肺泡灌洗液(BALF)中白细胞总数,瑞氏吉姆萨染色计数嗜酸性粒细胞数(EOS),HE染色和PAS染色法观察小鼠肺组织病理变化,ELISA法测定血清中IL-4、IgE及IFN-γ水平,16S rRNA分析小鼠肺部菌群。结果:与模型组相比,酪酸梭菌组白细胞总数、EOS炎症细胞显著降低(P<0.05),肺部炎症细胞浸润及杯状细胞增生明显减轻,血清中IL-4、IgE水平明显降低(P<0.05),IFN-γ水平明显升高(P<0.05),维持Th1/Th2平衡;小鼠肺部Proteobacteria及Escherichia-Shigella菌丰度显著降低,且相关性分析表明,IL-4、IgE水平减少与Escherichia-Shigella丰度增加呈正相关(P<0.05,r>0.9)。结论:酪酸梭菌干预可能通过改变肺部菌群组成,调节免疫细胞及细胞因子,维持机体Th1/Th2平衡,从而减轻OVA诱导的过敏性哮喘肺部炎症。Objective:To explore the intervention mechanism of Clostridium butyricum on asthma from the perspective of immune inflammation and pulmonary flora,and to provide a new scheme for the prevention and treatment of asthma.Methods:Mice were randomly divided into Clostridium butyricum(CM)group,asthma model group(Model)and normal control group(Control),with 16 mice in each group.The model group and CM group were sensitized by ovalbumin(OVA)and stimulated by continuous atomization of 1%OVA solution to establish asthma mouse model,and the control group was replaced by normal saline.Mice in CM group were administrated with CM solution at 1×109 CFU/d.The total number of white blood cells in bronchoalveolar lavage fluid(BALF)was counted.Eosinophil number(EOS)was counted by Wright-Giemsa staining.The pathological changes of lung tissue were observed by HE staining and PAS staining.Serum levels of IL-4,IgE and IFN-γwere determined by ELISA.Mouse lung microflora was analyzed by 16S rRNA.Results:Compared with Model group,white blood cells and EOS inflammatory cells in CM group were significantly decreased(P<0.05),lung inflammatory cell infiltration and goblet cell proliferation were significantly reduced,serum IL-4 and IgE levels were significantly decreased(P<0.05),IFN-γlevels were significantly increased(P<0.05),and Th1/Th2 balance was maintained.The abundance of Proteobacteria and Escherichia-Shigella in the lung of mice were significantly decreased,and correlation analysis showed that the decrease of IL-4 and IgE levels were positively correlated with the increase of Escherichia-Shigella abundance(P<0.05,r>0.9).Conclusion:Clostridium butyricum intervention can change the composition of lung flora,regulate immune cells and cytokines,maintain Th1/Th2 balance,so as to reduce the OVA-induced pulmonary inflammation of allergic asthma.
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