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评估三碘甲状腺原氨酸治疗对肺纤维化小鼠肺部微生物组的影响。

Assessing the impact of triiodothyronine treatment on the lung microbiome of mice with pulmonary fibrosis.

机构信息

State Key Laboratory of Cell Differentiation and Regulation; Henan International Joint Laboratory of Pulmonary Fibrosis; Henan Center for Outstanding Overseas Scientists of Organ Fibrosis; Pingyuan Laboratory; College of Life Science , Henan Normal University, No.46 Jianshe Road, Xinxiang City, 453007, Henan, China.

Department of Physiology, Department of Fundamental Medicine, Changzhi Medical College, Changzhi, 046000, Shanxi, China.

出版信息

BMC Pulm Med. 2024 Aug 23;24(1):405. doi: 10.1186/s12890-024-03214-3.

DOI:10.1186/s12890-024-03214-3
PMID:39180004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11344337/
Abstract

BACKGROUND

Idiopathic pulmonary fibrosis (IPF), an interstitial lung disease, is characterized by the exacerbation of progressive pulmonary fibrosis (PF). IPF primarily affects older individuals and can lead to respiratory failure. This study aimed to assess the effects of triiodothyronine (T) treatment on the lung microbiome of mice with PF.

METHODS

Mice were perfused with bleomycin (BLM) to establish a PF model. Using a randomized design, 40 female specific pathogen-free (SPF) C57BL6/N mice were divided into four groups: saline, saline + T, BLM, and BLM + T. Histological morphology was assessed through Hematoxylin and Eosin staining as well as Masson's Trichrome staining. For the identification of lung bacteria, 16S rRNA gene sequencing was employed. An Enzyme-Linked Immunosorbent Assay was used to measure total T (TT), free T (FT, and reverse T (rT) levels in the peripheral serum.

RESULTS

T treatment ameliorated BLM-induced lung fibrosis and structural damage. The microbiome experienced a decrease in the abundance of Proteobacteria, Bacteroides, and Actinomycetes and an increase in the abundance of Firmicutes when exposed to BLM; however, T treatment reversed this effect. The four groups showed no significant difference in alpha microbiome diversity (P > 0.05). Serum concentrations of TT and FT were positively correlated with microbiome abundance (P < 0.05). Administration of T enhanced the microbiota in PF without affecting the diversity and biological functions of the microbiome (P > 0.05).

CONCLUSION

The administration of T demonstrated a favorable impact on the lung microbiota of mice afflicted with PF, thereby partially substantiating the potential role of T as a therapeutic agent in the management of PF.

摘要

背景

特发性肺纤维化(IPF)是一种间质性肺疾病,其特征是进行性肺纤维化(PF)的恶化。IPF 主要影响老年人,并可导致呼吸衰竭。本研究旨在评估三碘甲状腺原氨酸(T)治疗对 PF 小鼠肺部微生物组的影响。

方法

用博来霉素(BLM)灌洗小鼠建立 PF 模型。使用随机设计,将 40 只雌性无特定病原体(SPF)C57BL6/N 小鼠分为四组:生理盐水、生理盐水+T、BLM 和 BLM+T。通过苏木精和伊红染色以及 Masson 三色染色评估组织学形态。为了鉴定肺部细菌,使用 16S rRNA 基因测序。酶联免疫吸附试验用于测量外周血清中的总 T(TT)、游离 T(FT)和反向 T(rT)水平。

结果

T 治疗改善了 BLM 诱导的肺纤维化和结构损伤。当暴露于 BLM 时,微生物组中变形菌门、拟杆菌门和放线菌门的丰度减少,厚壁菌门的丰度增加;然而,T 治疗逆转了这种效应。四组的 alpha 微生物组多样性无显著差异(P>0.05)。血清 TT 和 FT 浓度与微生物组丰度呈正相关(P<0.05)。T 的给药增强了 PF 中的微生物群,而不影响微生物组的多样性和生物学功能(P>0.05)。

结论

T 的给药对 PF 小鼠的肺部微生物群产生了有利影响,部分证实了 T 作为 PF 治疗药物的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/0bae0b11f434/12890_2024_3214_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/097ce855408f/12890_2024_3214_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/0bae0b11f434/12890_2024_3214_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/252427269066/12890_2024_3214_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/dd4ac707e629/12890_2024_3214_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/8a5f06194622/12890_2024_3214_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/ed446dc99f42/12890_2024_3214_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/3e7de2735451/12890_2024_3214_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/097ce855408f/12890_2024_3214_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcb3/11344337/0bae0b11f434/12890_2024_3214_Fig8_HTML.jpg

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