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中华细胞与干细胞杂志(电子版) ›› 2019, Vol. 09 ›› Issue (02) : 72 -78. doi: 10.3877/cma.j.issn.2095-1221.2019.02.002

论著

体育运动对冠心病患者内皮祖细胞血管内皮损伤修复能力的改善作用研究
胡厚如1, 董兵2, 何江2, 余冰波2, 张小宇2, 夏文豪2,()   
  1. 1. 435100 大冶市中医医院血液透析科
    2. 510080 广州,中山大学附属第一医院高血压血管病科 卫生部辅助循环重点实验室
  • 收稿日期:2018-11-23 出版日期:2019-04-01
  • 通信作者: 夏文豪
  • 基金资助:
    国家自然科学基金(81671379,81200249); 广东省科技计划项目(2017A020215085,2016A020215056)

Physical exercise enhances endothelial repair capacity of endothelial progenitor cells and improves endothelial function and arterial elasticity in patient with coronary heart disease

Houru Hu1, Bing Dong2, Jiang He2, Bingbo Yu2, Xiaoyu Zhang2, Wenhao Xia2,()   

  1. 1. Department of Hemodialysis, the Traditional Chinese Medicine Hospital of Daye, Daye 435100, China
    2. Department of Hypertension and Vascular Disease, the First Affiliated Hospital, Sun Yat-Sen University/Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China
  • Received:2018-11-23 Published:2019-04-01
  • Corresponding author: Wenhao Xia
  • About author:

    Hu Houru and Dong Bing are the first authors who contributed equally to the article

引用本文:

胡厚如, 董兵, 何江, 余冰波, 张小宇, 夏文豪. 体育运动对冠心病患者内皮祖细胞血管内皮损伤修复能力的改善作用研究[J]. 中华细胞与干细胞杂志(电子版), 2019, 09(02): 72-78.

Houru Hu, Bing Dong, Jiang He, Bingbo Yu, Xiaoyu Zhang, Wenhao Xia. Physical exercise enhances endothelial repair capacity of endothelial progenitor cells and improves endothelial function and arterial elasticity in patient with coronary heart disease[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(02): 72-78.

目的

探讨体育运动对冠心病(CHD)患者内皮祖细胞(EPCs)内皮损伤修复能力的影响及其可能的机制。

方法

选取广州中山大学第一附属医院收治的68例符合冠心病临床诊断标准的受试者作为研究对象,随机分为对照组和实验组。实验组和对照组均进行常规药物治疗,同时实验组参与3个月踏车运动试验(每周3次,30 min/次,MET为4.5),对照组不进行运动干预。通过Boyden改良小室法和观察荧光标记的EPCs(CM-DiI-EPCs)黏附到内皮细胞单层数量来分别检测EPCs的迁移能力和黏附能力;利用裸鼠颈动脉内皮损伤模型,肱动脉血流介导的血管舒张功能(FMD)和肱-踝动脉脉搏波传导速度(PWV),分别研究EPCs在体内皮损伤修复能力、血管内皮功能和动脉硬度。统计学采用单因素方差和Pearson法相关性分析。

结果

3个月的体育锻炼后,实验组受试者外周血EPCs体外的迁移(运动后:52.5±8.9;运动前:30.6±5.4;t = 3.767,P = 0.013)、黏附能力明显提高(运动后:48.2±7.6;运动前:30.5±4.8;t = 4.311,P < 0.001),移植后裸鼠颈动脉内皮损伤在体的内皮化面积增大(运动后:55.2%±9.1%;运动前:35.9%± 4.9%;t = 5.315,P = 0.012);内皮功能FMD改善(运动前:5.9%± 2.1%;运动后:8.1%± 2.6%;t = 3.253,P < 0.001);动脉弹性PWV下降[运动前:(1618±160.2)cm/s;运动后:(1456±125)cm/s;t = 2.781,P = 0.014];Pearson相关分析结果显示,升高的FMD、下降的PWV分别与增加的EPCs再内皮化面积呈正相关,而对照组以上指标无明显改变。

结论

体育运动明显改善冠心病患者血管内皮功能,提高动脉弹性,部分机制可能与循环EPCs介导的内皮损伤修复能力增强相关。

Objective

To investigate the effect of physical exercise on the endothelial repair capacity of endothelial progenitor cells (EPCs) in patients with coronary heart disease (CHD) .

Methods

Sixty-eight CHD subjects (diagnosed by coronary angiography) were enrolled into the study. All subjects were randomly divided into a control group (67.5±5.8 years old, n = 32) and a treatment group (68.3±7.1 years old, n = 36). Subjects of the treatment group were undergone a 3 months treadmill exercise test intervention (30 min/d for 3 days per week, MET 4.5) except conventional drugs treatment, and the control group were just treated by conventional drugs treatment. The migration of EPCs was detected by modified Boyden chamber assay and the adhesion of EPCs was calculated by the number of fluorescently labeled EPCs adhered to human umbilical vein endothelial cells before and after treadmill exercise test. Nude mice carotid arterial intimal injury model was used to observe reendothelialization capacity in vivo of EPCs. Flow- mediated dilatation (FMD) and Pulse wave velocity (PWV) of subjects were observed before and after 3-month treadmill exercise test, with one-way ANNOVA and PearsonCorrelation analysis.

Results

The migration and adhesion function were improved, and the reendothelialization area of EPCs was bigger (after exercise: 53.4%±9.1% vs before exercise: 35.9%±4.9%; P < 0.01) ; FMD level was higher (after exercise: 8.1%±2.6% vs before exercise: 5.8%±2.2%; P < 0.001) ; PWV level was lower[after exercise: (1618±160.2) cm/s vs before exercise: (1456±125) cm/s; P < 0.01] in healthy elderly subjects after 3-month physical exercise than before exercise. Pearson correlation analysis showed that improved FMD and decreased PWV were positively correlated with the increased reendothelialization area of EPCs. However, the FMD, PWV, in vitro and in vivo functional activities of EPCs from the control group have no obvious change.

Conclusion

Physical exercise obviously improved endothelial function and arterial elasticity in CHD, which may partly resulted from enhancement of endogenous endothelial repair capacity of EPCs.

表1 冠心病受试者基线资料( ± s
表2 健康受试者和冠心病受试者运动前后内皮功能和EPC功能检测( ± s
图1 荧光显微镜观察EPCs体外迁移实验(DAPI染细胞核,×40)注:a、b图分别为对照组和实验组运动前EPCs迁移,c、d图分别为对照组和实验组运动后EPCs迁移。可见对照组的EPCs体外的迁移能力运动前后无差异,实验组患者运动后EPCs体外的迁移能力提高
图2 荧光显微镜观察EPCs体外黏附实验(DAPI染细胞核,×40)注:a、b图分别为对照组和实验组运动前EPCs黏附实验,c、d图分别为对照组和实验组运动后EPCs黏附实验。可见实验组受试者运动后EPCs数量较自身运动前增多,对照组改变无明显差异
图3 对照组与实验组运动前后EPCs再内皮化面积比较注:EPCs为内皮祖细胞;PBS为磷酸盐缓冲液。与PBS组比较,*P < 0.001;与实验组运动前相比,**P < 0.01
图4 裸鼠颈总动脉内皮伊文思蓝染色结果注:PBS为磷酸盐缓冲液
图5 运动前后FMD差值与EPCs移植注射后再内皮化面积差值的相关性(n = 36)注:FMD为血流介导的血管舒张功能;EPCs为内皮祖细胞
图6 运动前后PWV差值与EPCs移植注射后再内皮化面积差值的相关性(n = 36)注:PWV为脉搏波传导速度;EPCs为内皮祖细胞
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