切换至 "中华医学电子期刊资源库"
高级检索
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:
全文 ( ) 下载PDF ( ) 导出引用
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
1
郭帅，曾志勇，杨胜生，等. 骨髓间充质干细胞对海水淹溺致急性肺损伤治疗作用的研究进展[J]. 中国胸心血管外科临床杂志，2015, 22(4): 375-379.
2
王博荣，李鹏程，刘菲，等. β-catenin过表达的间充质干细胞对改善海水吸入型肺损伤治疗效果的研究[J/CD]. 中华肺部疾病杂志(电子版), 2018, 11(1): 20-24.
3
罗建峰，吴华杰，石曌玲，等. 1，25-二羟维生素D3抑制RhoA/ROCK通路减轻幼鼠海水淹溺型肺损伤的实验研究[J/CD]. 中华肺部疾病杂志(电子版), 2015, 8(5): 565-568.
4
谭远辉，刘健，朱四海，等. 姜黄素对海水吸入性肺损伤的防治作用[J]. 临床麻醉学杂志，2016, 32(1): 61-64.
5
Ohishi M,Schipani E. Bone marrow mesenchymal stem cells [J]. J Cell Biochem, 2010, 109(2): 277-282.
6
Zhou J,Jiang L,Long X, et al. Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats[J]. J Cell Mol Med, 2016, 20(9): 1706-1717.
7
Zhang J,Shao Y,He D, et al. Evidence that bone marrow-derived mesenchymal stem cells reduce epithelial permeability following phosgene-induced acute lung injury via activation of wnt3a protein-induced canonical wnt/β-catenin signaling[J]. Inhal Toxicol, 2016, 28(12): 572-579.
8
Li D,Pan X,Zhao J, et al. Bone marrow mesenchymal stem cells suppress acute lung injury induced by lipopolysaccharide through inhibiting the TLR2, 4/NF-κB pathway in rats with multiple trauma[J]. Shock, 2016, 45(6): 641-646.
9
Gupta N,Su X,Popov B, et al. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice[J]. J Immunol, 2007, 179(3): 1855-1863.
10
Li J,Guo W,Xiong M, et al. Effect of SDF-1 /CXCR4 axis on the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward lesion sites following spinal cord injury[J]. Int J Mol Med, 2015, 36(5): 1205-1214.
11
周长喜，钱桂生，王关嵩. 海水淹溺机制研究进展[J]. 人民军医，2008, 51(10): 630-631.
12
Mohi El-Din MM,Rashed LA,Mahmoud Haridy MA, et al. Impact of bone marrow-derived mesenchymal stem cells on remodeling the lung injury induced by lipopolysaccharides in mice[J]. Future Sci OA, 2017, 3(1): FSO162.
13
Liu HM,Liu YT,Zhang J, et al. Bone marrow mesenchymal stem cells ameliorate lung injury through anti-inflammatory and antibacterial effect in COPD mice[J]. J Huazhong Univ Sci Technolog Med Sci, 2017, 37(4): 496-504.
14
Xia C,Chang P,Zhang Y, et al. Therapeutic effects of bone marrow-derived mesenchymal stem cells on radiation-induced lung injury[J]. Oncol Rep, 2016, 35(2): 731-738.
15
Luan Y,Ding W,Ju ZY, et al. Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia[J]. Mol Med Rep, 2015, 11(3): 1945-1950.
16
Li J,Zhou J,Zhang D, et al. Bone marrow-derived mesenchymal stem cells enhance autophagy via PI3K/AKT signalling to reduce the severity of ischaemia/reperfusion-induced lung injury[J]. J Cell Mol Med, 2015, 19(10): 2341-2351.
17
Yang H,Wen Y,Hou-you Y, et al. Combined treatment with bone marrow mesenchymal stem cells and methylprednisolone in paraquat-induced acute lung injury[J]. BMC Emerg Med, 2013, 13 Suppl 1: S5.
18
Liu QP,Zhou DX,Sun L, et al. Bone marrow mesenchymal stem cells ameliorates seawater-exposure-induced acute lung injury by inhibiting autophagy in lung tissue[J]. Patholog Res Int, 2014, 2014: 104962.
19
Gupta N,Su X,Popov B, et al. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice[J]. J Immunol, 2007, 179(3): 1855-1863.
20
王倩梅，朱朝娟，徐云云，等. CXCR4高表达骨髓间充质干细胞对百草枯中毒肺损伤大鼠的治疗作用[J]. 解放军医药杂志，2017, 29(8): 1-5.
[1] 梁哲浩, 方明笋, 胡弘毅, 陶涛, 徐孝平, 孙华琴. 基于生物信息学分析筛选脓毒症诱导急性肺损伤的关键基因[J]. 中华危重症医学杂志(电子版), 2022, 15(05): 360-366.
[2] 吴芳伟, 安向丽, 谢晓宁. 调控骨桥蛋白介导的中性粒细胞浸润减轻脓毒症小鼠肺损伤的研究[J]. 中华危重症医学杂志(电子版), 2022, 15(03): 220-225.
[3] 沈纵, 魏晨如, 朱邦晖, 包郁露, 伍国胜, 孙瑜. 间充质干细胞治疗吸入性损伤的动物实验研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(02): 180-183.
[4] 蔡维霞, 曹涛, 赵明, 肖丹, 贾艳慧, 王璟, 张月, 王克甲, 韩军涛, 胡大海. Notch信号通路对烧伤大鼠血清诱导的肺血管内皮细胞细胞间黏附分子-1的影响[J]. 中华损伤与修复杂志(电子版), 2022, 17(04): 292-299.
[5] 熊欢庆, 李玉娟, 陈键, 刘刚, 李志超, 金发光. 丹参酮IIA及苦参碱组方对脂多糖致小鼠急性肺损伤的协同保护作用[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 455-459.
[6] 李埝, 赵建军, 张建勇, 赵睿桢. hAMSCs调控MAPK信号通路对急性肺损伤AQP1的影响[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 156-163.
[7] 董红雪, 沈玥, 鲁静, 帅维正, 高苗莉, 陶莎. 俯卧位机械通气在慢性阻塞性肺疾病急性加重期的临床应用[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 263-265.
[8] 伍正彬, 邵世锋, 李阳, 王耀丽. 高原爆炸性肺损伤院前急救和早期救治策略[J]. 中华肺部疾病杂志(电子版), 2022, 15(05): 746-749.
[9] 吴志军, 田伟, 任欢, 董文. 非小细胞肺癌调强放疗致放射性肺损伤风险的预测[J]. 中华肺部疾病杂志(电子版), 2022, 15(04): 560-562.
[10] 周艳群, 陈鹏, 刘增慧, 毛晶晶, 黎耀和. 多发性骨髓瘤患者骨髓间充质干细胞衰老关键基因和通路的生物信息学分析与验证[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(05): 274-281.
[11] 刘然然, 方倩倩, 唐泽文. 周围神经损伤对骨髓间充质干细胞增殖及成骨分化影响的研究[J]. 中华神经创伤外科电子杂志, 2023, 09(01): 7-11.
[12] 常炜, 刘玲. 呼吸驱动及呼吸努力床旁评估的研究进展[J]. 中华重症医学电子杂志, 2023, 09(01): 25-29.
[13] 阳莹, 崔亚梅, 邵强, 赵宁, 陶文强, 陈家泉, 徐泽尧, 钱克俭, 刘芬. 线粒体自噬对肺泡巨噬细胞焦亡的调控作用及其机制[J]. 中华重症医学电子杂志, 2023, 09(01): 69-77.
[14] 刘玲, 赵慧颖, 李绪言, 程渊, 罗巧侠, 俞云, 杨毅, 邱海波. 新型冠状病毒肺炎患者自主呼吸努力的床旁监测方法[J]. 中华重症医学电子杂志, 2022, 08(04): 367-370.
[15] 单秋洁, 孙立柱, 徐宜全, 王之霞, 徐妍, 马浩, 刘田田. 中老年食管癌患者调强放射治疗期间放射性肺损伤风险模型构建及应用[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 388-393.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号