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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2019, Vol. 12 ›› Issue (01) : 28 -33. doi: 10.3877/cma.j.issn.1674-6902.2019.01.005

所属专题： 文献；

论著

SDF-1α/CXCR4信号促进骨髓间充质干细胞对海水吸入性肺损伤的治疗作用
宋斯迪1, 鲁曦2, 金发光2,†(), 梁源3, 鱼高乐2   
  1. 1. 710043　西安，陕西省第四人民医院呼吸内科
    2. 710038　西安，空军军医大学（第四军医大学）唐都医院呼吸内科
    3. 650032　昆明，昆明军区总医院
  • 收稿日期:2018-07-10 出版日期:2019-02-20
  • 通信作者: 金发光
  • 基金资助:
    军队保健项目(14BJZ55); 国家自然科学基金资助项目(81741104)

SDF-1α/CXCR4 signaling improves the therapeutic effect of bone marrow mesenchymal stem cells on seawater drowning induced acute lung injury

Sidi Song1, Xi Lu2, Faguang Jin2,†(), Yuan Liang3, Gaole Yu2   

  1. 1. Department of Respiratory Medicine, Fourth People′s Hospital of Shaanxi Province, Xi′an 710043, China
    2. Department of Respiratory Medicine, Tangdu Hospital, Air Force Medical University, Xi′an 710038, China
    3. The General hospital of Kunming Military Region, Kunming 650032, China
  • Received:2018-07-10 Published:2019-02-20
  • Corresponding author: Faguang Jin
  • About author:
    Corresponding author: Jin Faguang, Email:
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引用本文：

宋斯迪, 鲁曦, 金发光, 梁源, 鱼高乐. SDF-1α/CXCR4信号促进骨髓间充质干细胞对海水吸入性肺损伤的治疗作用[J]. 中华肺部疾病杂志(电子版), 2019, 12(01): 28-33.

Sidi Song, Xi Lu, Faguang Jin, Yuan Liang, Gaole Yu. SDF-1α/CXCR4 signaling improves the therapeutic effect of bone marrow mesenchymal stem cells on seawater drowning induced acute lung injury[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2019, 12(01): 28-33.

目的

探讨骨髓间充质肝细胞(BMMSCs)对海水吸入性肺损伤的修复及SDF-1α/CXCR4信号在其中的作用。

方法

分离培养BMMSCs并建立大鼠海水吸入性肺损伤模型，Transwell实验检测BMMSCs迁移，采用CXCR4阻断剂AMD3100预处理BMMSCs和SDF-1α肺部给药调控SDF-1α/CXCR4信号，采用real-time PCR和western blot检测肺组织SDF-1α和CXCR4表达，行肺组织活检HE染色和肺湿干比检测肺损伤。

结果

BMMSCs可改善海水吸入引起的肺组织渗出、水肿和炎症细胞浸润，降低肺湿干比，AMD3100预处理可抑制BMMSCs的上述治疗作用。体外SDF-1α可促进BMMSCs的迁移，而SDF-1α肺部给药可促进BMMSCs对海水吸入性肺损伤的修复。

结论

BMMSCs可有效治疗海水吸入性肺损伤，SDF-1α/CXCR4信号可促进BMMSCs向损伤肺组织迁移、定植，进而促进海水吸入性肺损伤的修复。

关键词: 海水, 肺损伤, 骨髓间充质干细胞, 基质细胞衍生因子-1, CXC趋化因子受体4
Objective

To investigate the therapeutic effect of bone marrow mesenchymal stem cells (BMMSCs) on seawater drowning induced acute lung injury (SWD-ALI) and the role of SDF-1α/CXCR4 signaling.

Methods

BMMSCs were isolated and cultured and a rat model of SWD-ALI was established. Then, the BMMSCs migration was tested by transwell, the SDF-1α/CXCR4 signaling was regulated by AMD3100 pretreatment and lung delivery of SDF-1α, the expressions of SDF-1α and CXCR4 in lung were detected by real-time PCR and western blot, and the HE staining and wet/dry ratio were used to determine the lung injury.

Results

BMMSCs alleviates the alveoli exudation, edema and inflammatory cell infiltration induced by seawater inhalation, which was abolished by the CXCR4 blocker. SDF-1α promoted the migration of BMMSCs in vitro, and facilitated the repairing action of BMMSCs to the SWD-ALI in vivo.

Conclusion

BMMSCs could effectively therapy the SWD-ALI, and SDF-1α/CXCR4 signaling play important roles in promoting the BMMSCs migration to the injured lung and subsequently repairing process.

Key words: Seawater, Lung injury, Bone marrow mesenchymal stem cells, SDF-1α, CXCR4
表1 real-time PCR引物序列
名　称 序　列
SDF-1α F TCTGCATCAGTGACGGTAAG
SDF-1α R TAAGGCTTTGTCCAGGTA
CXCR4 F TCTTCTTGACTGGCATAGTGG
CXCR4 R GCTGTAAAGGTTGACGGTGTA
β-actin F GGAGATTACTGCCCTGGCTCCTAGC
β-actin R GGCCGGACTCATCGTACTCCTGCTT
图1 骨髓间充质干细胞鉴定；注：A：光镜观察骨髓间充质干细胞；B：流式细胞检测IgG阴性对照；C：流式细胞检测表面标志物CD29
图2 SDF-1α/CXCR4对骨髓间充质干细胞迁移的影响；注：A：Transwell微孔膜结晶紫染色；B：迁移BMMSC细胞数统计；*，**：P<0.05和0.01与"AMD3100(－)，SDF-1α (0)"组比较；##：P<0.01与"AMD3100(＋)，SDF-1α (0)"组比较；&&：对应组比较P<0.01
图3 海水吸入和BMMSCs治疗对肺组织SDF-1α和CXCR4表达的影响；注：A：RealPCR海水吸入和BMMSCs治疗对CXCR4 mRNA表达的影响；B：海水吸入和BMMSCs治疗对SDF-1α mRNA表达的影响；C：Western blot检测海水吸入和BMMSCs治疗对CXCR4和SDF-1α蛋白表达的影响；*，**：P<0.05和0.01与对照相比；##：P<0.05与对应组相比
图4 海水吸入和BMMSCs治疗对肺组织病理和湿干重比的影响；注：A：海水吸入和BMMSCs治疗后肺组织HE染色(×100)；B：海水吸入和BMMSCs治疗后肺湿干重比统计；*，**：P<0.05和0.01与对照相比；#，##：P<0.05和0.01与对应组相比；n.s.：无统计学差异
图5 SDF-1α对BMMSCs治疗海水吸附性肺损伤的影响；注：A：BMMSCs及复合SDF-1α治疗后肺组织HE染色(×100)；B：BMMSCs及复合SDF-1α治疗后肺湿干重比统计；*，**：P<0.05和0.01与对照相比；#，##：P<0.05和0.01与对应组相比
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