基于肠道菌群调控肾素-血管紧张素系统在支气管哮喘中的作用机制  

The mechanism of regulating renin angiotensin system in bronchial asthma based on intestinal flora

作　　者：唐珍 孟宝 朱玉林[1,3] TANG Zhen;MENG Bao;ZHU Yulin(Department of Pediatrics,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China;不详)

机构地区：[1]安徽医科大学第一附属医院儿科,安徽合肥230022 [2]安徽医科大学第一附属医院感染科 [3]首都医科大学附属北京儿童医院,国家呼吸系统疾病临床医学研究中心

出　　处：《中国微生态学杂志》2024年第5期497-503,共7页Chinese Journal of Microecology

基　　金：安徽医科大学基础与临床合作提升计划(2019xkjT024)。

摘　　要：目的探究肾素-血管紧张素系统在哮喘患者肠道微生态中的作用。方法将20只Balb/c雌性小鼠随机分为对照组、哮喘组、抗生素组和鼠李糖乳酪杆菌(LGG)组,每组5只。通过卵白蛋白致敏并激发的方法建立哮喘小鼠模型,小鼠饮用水中添加新鲜广谱抗菌药物进行肠道菌群耗竭。采用苏木精―伊红染色观察各组小鼠肺组织的病理变化;流式细胞术检测脾中Th1/Th2比例;RT-PCR法检测肺组织中GATA3、T-bet、ACE、ACE2、AngⅡ、AT1R、AT2R的mRNA表达以及细胞因子受体IL-4、IL-5、IL-13、IFN-γ的mRNA表达水平;收集粪便样本进行16S rRNA基因高通量测序,分析肠道菌群组成与多样性。结果与对照组相比,哮喘组小鼠气道炎症程度显著增加;脾脏中Th1/2比例升高;肺组织中炎症因子受体IL-4、IL-5、IL-13 mRNA表达升高,IFN-γmRNA表达降低,GATA3、ACE、AngⅡ、AT1R、AT2R的mRNA表达升高,T-bet、ACE2 mRNA表达降低;肠道微生物中门、纲、目、科、属、种水平无显著差异。相比于哮喘组,抗生素组与LGG组均能减轻哮喘小鼠气道炎症,抑制ACE/AngⅡ/AT1R轴,但LGG组效果更为显著,且肠道菌群多样性程度更高。结论补充LGG可以保护肠道微生态的平衡,其产生的代谢物可能经血液循环,通过抑制ACE/AngⅡ/AT1R轴,抑制Th2相关细胞因子的释放,对哮喘产生治疗作用,其中的具体机制仍需进一步验证。Objective To explore the role of the renin angiotensin system in asthma and intestinal microecology.Methods Twenty Balb/c female mice were randomized into control group,asthma group,antibiotics group and Lacticaseibacillus rhamnosus(LGG)group,5 in each group.The asthma mouse model was established through ovalbumin sensitization and excitation,and fresh broad-spectrum antimicrobial drugs were added into the drinking water for intestinal flora depletion.Hematoxylin-eosin staining was used to observe the pathological changes in the lung tissues of mice;flow cytometry to detect the Th1/2 ratio in the spleen;RT-PCR to detect the mRNA expressions of GATA3,T-bet,ACE,ACE2,AngⅡ,AT1R,AT2R and the cytokine receptors IL-4,IL-5,IL-13 and IFN-γin the lung tissue.Feces were collected for 16S rRNA gene high-throughput sequencing to analyze the composition and diversity of intestinal flora.Results Compared with the control group,the asthma group showed significant increases in the degree of airway inflammation;the ratio of Th1/2 elevated in the spleen;the mRNA expressions of IL-4,IL-5,IL-13,GATA3,ACE,AngⅡ,AT1R and AT2R in lung tissue were significantly higher,but those of IFN-γ,T-bet and ACE2 were significantly lower in the asthma group than those in the control group,respectively.There were almost no differences in the levels of phylum,class,order,family,genus and species of gut microorganisms.Compared with the asthma group,both the antibiotic group and the LGG group were able to reduce airway inflammation and inhibit the ACE/AngⅡ/AT1R axis,but the LGG group showed a better effect and a higher degree of intestinal flora diversity.Conclusion Supplementation of LGG can maintain the balance of intestinal microecology,and the metabolites it produces may circulate through the bloodstream and have a therapeutic effect on asthma by inhibiting the ACE/AngⅡ/AT1R axis and inhibiting the release of Th2-associated cytokines.The exact mechanisms involved still need to be further verified.

关 键 词：哮喘 肠道菌群 鼠李糖乳酪杆菌 肾素-血管紧张素系统 

分 类 号：R725.6[医药卫生—儿科]