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胡颓子乙素通过调节肺 Th1/Th2 平衡和肠道微生物群来保护卵清蛋白诱导的哮喘小鼠的肺部病理变化。

Sodium houttuyfonate modulates the lung Th1/Th2 balance and gut microbiota to protect against pathological changes in lung of ovalbumin-induced asthmatic mice.

机构信息

College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

School of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, China.

出版信息

J Asthma. 2024 Dec;61(12):1759-1771. doi: 10.1080/02770903.2024.2380525. Epub 2024 Jul 26.

Abstract

OBJECTIVE

The gut-lung axis involves microbial and product interactions between the lung and intestine. Antibiotics for chronic asthma can cause intestinal dysbiosis, disrupting this axis. Sodium houttuyfonate (SH) has diverse biological activities, including modifying gut microbiota, antibacterial, and anti-inflammatory. This study aims to explore the relationship between SH, CD4+ T cells, and gut microbiota.

METHODS

Allergic asthma was experimentally induced in mice through injection and inhalation of ovalbumin. After the administration of different amounts of SH, ELISA was utilized to ascertain the levels of inflammatory cytokines in the serum, flow cytometry was used to examine the levels of Th1/Th2 cytokines in CD4+ cells from lung tissues. The expression of T-bet and GATA3 in lung tissue was determined by Western blotting and quantitative real-time PCR assay. Gut microbiota was determined by 16S rRNA gene sequencing.

RESULTS

The results showed that SH can alleviate pulmonary injury in asthmatic mice, reducing serum levels of IL-4, IL-5, and IL-13 while simultaneously increasing IFN-γ. Furthermore, SH has been observed to modulate the balance of Th1/Th2 cells by up-regulating the mRNA and protein expression of T-bet but down-regulating GATA3 in the lung tissues of asthmatic mice, thereby promoting the differentiation of Th1 cells. Additionally, SH can regulate the variety and composition of gut microbiota especially genus in asthmatic mice.

CONCLUSION

SH can alleviate asthma through the regulation of Th1/Th2 cells and gut microbiota.

摘要

目的

肠-肺轴涉及肺和肠道之间的微生物和产物相互作用。用于慢性哮喘的抗生素会引起肠道菌群失调,破坏这一轴。虎耳草素钠(SH)具有多种生物学活性,包括调节肠道微生物群、抗菌和抗炎作用。本研究旨在探讨 SH、CD4+T 细胞与肠道微生物群之间的关系。

方法

通过注射和吸入卵清蛋白在小鼠中诱发过敏性哮喘。在给予不同剂量的 SH 后,采用 ELISA 法测定血清中炎症细胞因子的水平,采用流式细胞术测定肺组织中 CD4+细胞中 Th1/Th2 细胞因子的水平。采用 Western blot 和实时定量 PCR 法测定肺组织中 T-bet 和 GATA3 的表达。通过 16S rRNA 基因测序测定肠道微生物群。

结果

结果表明,SH 可减轻哮喘小鼠的肺损伤,降低血清中 IL-4、IL-5 和 IL-13 的水平,同时增加 IFN-γ。此外,SH 被观察到通过上调哮喘小鼠肺组织中 T-bet 的 mRNA 和蛋白表达,同时下调 GATA3,调节 Th1/Th2 细胞的平衡,从而促进 Th1 细胞的分化。此外,SH 可以调节哮喘小鼠肠道微生物群的种类和组成,特别是属。

结论

SH 可通过调节 Th1/Th2 细胞和肠道微生物群来缓解哮喘。

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