中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (31): 8054-8059.doi: 10.12307/2026.855

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

骨髓间充质干细胞外泌体改善博来霉素诱导的小鼠肺纤维化

黄  莺，徐  芳，王爱利，袁文胜   

  1. 武汉市第一医院(武汉市中西医结合医院)，湖北省武汉市  430022
  • 收稿日期:2025-09-20 接受日期:2026-01-18 出版日期:2026-11-08 发布日期:2026-05-21
  • 通讯作者: 袁文胜，硕士，副主任医师，武汉市第一医院(武汉市中西医结合医院)，湖北省武汉市 430022
  • 作者简介:黄莺，女，1981年生，硕士，副主任医师，主要从事间质性肺疾病研究。
  • 基金资助:
    湖北省自然科学基金-面上项目(2024AFB1032)，项目负责人：王爱利

Bone marrow mesenchymal stem cell exosomes improve bleomycin-induced mouse pulmonary fibrosis

Huang Ying, Xu Fang, Wang Aili, Yuan Wensheng   

  1. Wuhan First Hospital (Wuhan Integrated Traditional Chinese and Western Medicine Hospital), Wuhan 430022, Hubei Province, China
  • Received:2025-09-20 Accepted:2026-01-18 Online:2026-11-08 Published:2026-05-21
  • Contact: Yuan Wensheng, MS, Associate chief physician, Wuhan First Hospital (Wuhan Integrated Traditional Chinese and Western Medicine Hospital), Wuhan 430022, Hubei Province, China
  • About author:Huang Ying, MS, Associate chief physician, Wuhan First Hospital (Wuhan Integrated Traditional Chinese and Western Medicine Hospital), Wuhan 430022, Hubei Province, China
  • Supported by:
    Hubei Provincial Natural Science Foundation-General Program, No. 2024AFB1032 (to WAL)

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摘要：

文题释义：

骨髓间充质干细胞外泌体：是由骨髓间充质干细胞分泌的纳米级囊泡，具有与骨髓间充质干细胞相似的遗传物质和生物学功能，免疫原性较低，粒径小且安全性高。
转化生长因子β1/Smad3信号通路：是调控细胞增殖分化、炎症、细胞凋亡以及组织纤维化等病理生理过程的关键信号通路，抑制转化生长因子β1/Smad3信号通路可缓解炎症和胶原沉积，进而延缓肺纤维化的发生发展。

摘要
背景：间充质干细胞外泌体具有与间充质干细胞相似的生物学功能且安全性高，可用于纤维化相关疾病的治疗，但是治疗肺纤维化的机制尚不明确。
目的：探究骨髓间充质干细胞外泌体对博来霉素诱导小鼠肺纤维化的影响及机制。
方法：提取C57BL/6J小鼠骨髓间充质干细胞及其外泌体并进行鉴定。将30只C57BL/6J小鼠随机分为对照组、模型组和外泌体组，每组10只，模型组和外泌体组经气管插管滴注5 mg/kg博来霉素构建肺纤维化模型，滴注博来霉素后第7天，外泌体组小鼠尾静脉给予100 μL0.1 mg/mL骨髓间充质干细胞外泌体，1次/d，连续2周。治疗结束后，检测小鼠肺功能指标气道狭窄指数、呼吸频率和潮气量，苏木精-伊红染色和Masson染色检测小鼠肺组织损伤及纤维化情况，酶联免疫吸附实验检测小鼠血清羟脯氨酸、白细胞介素1β、转化生长因子β1和肿瘤坏死因子α水平，实时荧光定量PCR检测小鼠肺组织α-平滑肌肌动蛋白、胶原蛋白 Ⅰ和纤连蛋白 mRNA表达，蛋白质印迹检测小鼠肺组织转化生长因子β1表达及Smad3磷酸化水平。

结果与结论：与对照组相比，模型组小鼠气道狭窄指数显著增加(P < 0.05)，呼吸频率和潮气量显著降低(P < 0.05)，α-平滑肌肌动蛋白、胶原蛋白Ⅰ和纤连蛋白 mRNA表达显著上调(P < 0.05)，羟脯氨酸、白细胞介素1β、转化生长因子β1和肿瘤坏死因子α水平显著增加(P < 0.05)，转化生长因子β1蛋白表达及Smad3磷酸化水平显著上调(P < 0.05)。与模型组相比，外泌体组小鼠肺损伤及纤维化水平显著缓解，气道狭窄指数显著降低(P < 0.05)，呼吸频率和潮气量显著升高(P < 0.05)，α-平滑肌肌动蛋白、胶原蛋白Ⅰ和纤连蛋白 mRNA表达显著下调(P < 0.05)，羟脯氨酸、白细胞介素1β、转化生长因子β1和肿瘤坏死因子α水平显著降低(P < 0.05)，转化生长因子β1蛋白表达及Smad3磷酸化水平显著降低(P < 0.05)。结果表明：骨髓间充质干细胞外泌体通过抑制转化生长因子β1/Smad3信号通路改善博来霉素诱导的小鼠肺纤维化。

https://orcid.org/0009-0006-1364-9169(黄莺)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 骨髓间充质干细胞, 外泌体, 博来霉素, 小鼠, 肺纤维化, 炎症, 转化生长因子β1/Smad3信号通路, 机制

Abstract: BACKGROUND: Mesenchymal stem cell exosomes have similar biological functions to mesenchymal stem cells and high safety, and can be used for the treatment of fibrosis-related diseases. However, the mechanisms underlying their therapeutic effects on pulmonary fibrosis remain unclear.
OBJECTIVE: To investigate the function and mechanism of bone marrow mesenchymal stem cell exosomes affecting bleomycin-induced pulmonary fibrosis in mice. 
METHODS: Bone marrow mesenchymal stem cells and their exosomes were extracted from C57BL/6J mice and characterized. Thirty C57BL/6J mice were randomly divided into three groups: control group, model group, and exosome group (10 mice per group). The model group and exosome group received intratracheal instillation of 5 mg/kg bleomycin to induce pulmonary fibrosis. On day 7 after bleomycin instillation, mice in the exosome group received 100 μL of 0.1 mg/mL bone marrow mesenchymal stem cell-derived exosomes via tail vein injection once daily for two weeks. After treatment, lung function indicators (airway narrowing index, respiratory rate, and tidal volume) were measured. Hematoxylin-eosin staining and Masson staining were used to assess lung tissue damage and fibrosis. Enzyme-linked immunosorbent assay was used to detect serum levels of hydroxyproline, interleukin-1β, transforming growth factor-β1, and tumor necrosis factor-α. Real-time quantitative PCR was used to detect the mRNA expression of α-smooth muscle actin, collagen I, and fibronectin in lung tissue. Western blotting was used to detect the expression of transforming growth factor-β1 and the phosphorylation level of Smad3 in mouse lung tissue.
RESULTS AND CONCLUSION: Compared with the control group, the model group mice showed a significantly increased airway narrowing index (P < 0.05), significantly decreased respiratory rate and tidal volume (P < 0.05), significantly upregulated α-smooth muscle actin, collagen I, and fibronectin mRNA expression (P < 0.05), significantly increased levels of hydroxyproline, interleukin-1β, transforming growth factor β1, and tumor necrosis factor α (P < 0.05), and significantly increased transforming growth factor β1 protein expression and Smad3 phosphorylation levels (P < 0.05). Compared with the model group, the exosome group mice showed significantly alleviated lung injury and fibrosis, a significantly decreased airway narrowing index (P < 0.05), significantly increased respiratory rate and tidal volume (P < 0.05), significantly downregulated α-smooth muscle actin, collagen I, and fibronectin mRNA expression (P < 0.05), significantly decreased levels of hydroxyproline, interleukin-1β, transforming growth factor β1, and tumor necrosis factor α (P < 0.05), and significantly decreased transforming growth factor β1 protein expression and Smad3 phosphorylation levels (P < 0.05). The results indicate that bone marrow mesenchymal stem cell-derived exosomes inhibit the transforming growth factor β1/Smad3 signaling pathway to ameliorate bleomycin-induced pulmonary fibrosis in mice.

Key words: ">bone marrow mesenchymal stem cell, exosome, bleomycin, mouse, pulmonary fibrosis, inflammation, transforming growth factor-β1/Smad3 signaling pathway, mechanism

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