中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (7): 1363-1370.doi: 10.12307/2025.007

• 脂肪干细胞 adipose-derived stem cells • 上一篇    下一篇

8周运动预适应增强脂肪干细胞治疗心肌梗死大鼠的效果

娄  国1，张  敏2，付常喜3   

  1. 1江苏经贸职业技术学院，江苏省南京市   211168；2南京旅游职业学院，江苏省南京市   211100；3徐州工程学院体育学院，江苏省徐州市   221008
  • 收稿日期:2023-11-23 接受日期:2024-01-10 出版日期:2025-03-08 发布日期:2024-06-27
  • 通讯作者: 付常喜，在读博士，副教授，徐州工程学院体育学院，江苏省徐州市 221008
  • 作者简介:娄国，男，1979年生，山东省新泰市人，硕士，讲师，主要从事运动健康促进方面的研究。
  • 基金资助:
    江苏省社会科学基金项目(22TYD001)，项目负责人：付常喜

Exercise preconditioning for eight weeks enhances therapeutic effect of adipose-derived stem cells in rats with myocardial infarction

Lou Guo1, Zhang Min2, Fu Changxi3   

  1. 1Jiangsu Vocational Institute of Commerce, Nanjing 211168, Jiangsu Province, China; 2Nanjing Vocational College of Tourism, Nanjing 211100, Jiangsu Province, China; 3Department of Physical Education, Xuzhou University of Technology, Xuzhou 221008, Jiangsu Province, China
  • Received:2023-11-23 Accepted:2024-01-10 Online:2025-03-08 Published:2024-06-27
  • Contact: Fu Changxi, Doctoral candidate, Associate professor, Department of Physical Education, Xuzhou University of Technology, Xuzhou 221008, Jiangsu Province, China
  • About author:Lou Guo, Master, Lecturer, Jiangsu Vocational Institute of Commerce, Nanjing 211168, Jiangsu Province, China
  • Supported by:
    Jiangsu Provincial Social Science Foundation Project, No. 22TYD001 (to FCX)

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摘要：

文题释义：

脂肪源性间充质干细胞：简称脂肪干细胞，具有自我更新、增殖及多向分化潜能，可分泌多种促血管生成因子和抗凋亡因子。由于脂肪组织在人体内储量丰富并易于获得，因此脂肪干细胞是理想的种子细胞来源。干细胞作为心肌梗死的崭新疗法具有广阔的应用前景。

血管生成：指从已有的毛细血管或毛细血管后静脉发展而形成新的血管，是一个涉及多种细胞、多种分子的复杂过程，这一过程受促血管形成因子和抑制因子协调作用，其中血管内皮生长因子是最重要的血管形成刺激因子。心肌梗死后血管生成对于增加心肌血流灌注、抑制细胞凋亡、改善心脏重塑、提升梗死后心脏功能具有重要意义。


背景：干细胞移植是心肌梗死的崭新疗法，然而梗死区域极其恶劣的微环境造成干细胞存活率低下并导致远期疗效甚微。运动预适应是一种通过运动诱导机体产生内源性保护效应的方式，可作为心脏康复预防与治疗的新策略。
目的：评估运动预适应是否能够增强大鼠心肌梗死后脂肪干细胞移植的心脏保护效应，探讨血管生成在其中的作用机制。
方法：6周龄雄性SD大鼠随机分为对照组、造模组、干细胞组以及干细胞运动组。利用冠状动脉闭塞术制作急性心肌梗死模型，对照组同期行假手术；干细胞运动组于造模前进行8周有氧运动，造模后30 min进行脂肪干细胞移植；干细胞组仅进行脂肪干细胞移植。干细胞移植后1 d和7 d，利用免疫印迹法测定心肌总Akt(t-Akt)、磷酸化Akt(p-Akt)、血管内皮生长因子(VEGF)、总内皮型一氧化氮合酶(t-eNOS)和磷酸化内皮型一氧化氮合酶(p-eNOS)蛋白表达量，计算p-Akt/t-Akt和p-eNOS/t-eNOS比值；4周后利用彩色多普勒超声诊断系统检测心脏结构与功能以及心肌血流量，TTC染色法检测心肌梗死面积，Masson染色法检测心肌间质胶原沉积，免疫荧光染色法测定心肌毛细血管密度，TUNEL染色法评估心肌细胞凋亡。
结果与结论：①干细胞移植后4周：与对照组比较，造模组左心室缩短分数、左心室射血分数、心肌毛细血管密度和心肌血流量下降
(P < 0.05)，心肌梗死面积、胶原容积分数和细胞凋亡增加(P < 0.05)；与造模组比较，干细胞组上述指标(除左心室缩短分数和左心室射血分数外)得到改善(P < 0.05)；与干细胞组比较，干细胞运动组以上各参数进一步改善(P < 0.05)。②干细胞移植后1 d：与对照组比较，造模组t-Akt、p-Akt、VEGF、t-eNOS、p-eNOS蛋白表达量以及p-Akt/t-Akt、p-eNOS/t-eNOS比值均无显著性变化(P > 0.05)；与造模组比较，干细胞组上述指标均无显著性变化(P > 0.05)，干细胞运动组磷酸化p-Akt蛋白表达量以及p-Akt/t-Akt比值上调(P < 0.05)。③干细胞移植后7 d：与对照组比较，造模组p-Akt、VEGF、p-eNOS蛋白表达量以及p-Akt/t-Akt、p-eNOS/t-eNOS比值下降(P < 0.05)；与造模组比较，干细胞组各参数均无显著性变化(P > 0.05)，干细胞运动组p-Akt、VEGF、p-eNOS蛋白表达量以及p-Akt/t-Akt、p-eNOS/t-eNOS比值升高(P < 0.05)。结果表明：运动预适应可增强脂肪干细胞对心肌梗死大鼠心脏重塑的治疗效果，其机制与促进心肌血管生成并增加血流灌注有关。

https://orcid.org/0000-0002-4369-0174 (娄国) 


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: 干细胞, 脂肪干细胞, 运动预适应, 心肌梗死, 血管生成, 心脏重塑, 血流灌注

Abstract: BACKGROUND: Stem cell transplantation is a novel therapy for myocardial infarction, but the extremely hostile microenvironment in the infarct area results in low survival rate of stem cells and little long-term effect. Exercise preconditioning is a way to induce endogenous protective effects through exercise, which can be used as a new strategy for prevention and treatment of cardiac rehabilitation.
OBJECTIVE: To evaluate whether exercise preconditioning potentiates the cardioprotective effects of adipose-derived stem cell transplantation following myocardial infarction in rats and to explore the mechanism of angiogenesis.
METHODS: Six-week-old male SD rats were randomly divided into control group, modeling group, stem cell group, and stem cell plus exercise group. Acute myocardial infarction model was made by coronary artery occlusion, and sham operation was performed in control group. The stem cell plus exercise group underwent aerobic exercise for 8 weeks before modeling, and adipose-derived stem cell transplantation was performed 30 minutes after modeling. The stem cell group performed only adipose-derived stem cell transplantation. One and seven days after stem cell transplantation, the expression levels of myocardial total Akt (t-Akt), phosphorylated Akt (p-Akt), vascular endothelial growth factor (VEGF), total endothelial nitric oxide synthase (t-eNOS), and phosphorylated endothelial nitric oxide synthase (p-eNOS) protein were measured by western blotting, and the ratios of p-Akt/t-Akt and p-eNOS/t-eNOS were calculated. At 4 weeks after stem cell transplantation, the heart structure and function as well as myocardial blood flow were detected by color Doppler ultrasound diagnostic system. Myocardial infarction area was measured by TTC staining. Myocardial interstitial collagen deposition was examined by Masson staining. Myocardial capillary density was detected by immunofluorescence staining, and myocardial apoptosis was measured by TUNEL staining. 
RESULTS AND CONCLUSION: (1) Four weeks after stem cell transplantation: Compared with control group, left ventricular shortening fraction, left ventricular ejection fraction, myocardial capillary density, and myocardial blood flow decreased (P < 0.05), myocardial infarction area, collagen volume fraction, and apoptosis increased (P < 0.05) in the modeling group. Compared with the modeling group, the above indexes (except for left ventricular fractional shortening and left ventricular ejection fraction) in the stem cell group improved (P < 0.05). Compared with the stem cell group, the above parameters were further improved in the stem cell plus exercise group (P < 0.05). (2) One day after stem cell transplantation: Compared with the control group, the protein expression of t-Akt, p-Akt, VEGF, t-eNOS, p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS had no significant changes in the modeling group (P > 0.05). Compared with the modeling group, there were no significant changes in the above indexes in the stem cell group (P > 0.05), and p-Akt protein expression and the ratio of p-Akt/t-Akt were up-regulated in the stem cell plus exercise group (P < 0.05). (3) Seven days after stem cell transplantation: Compared with the control group, the protein expression of p-Akt, VEGF, p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were decreased in the modeling group (P < 0.05). Compared with the modeling group, there were no significant changes in all parameters in the stem cell group (P > 0.05), and the protein expression of p-Akt, VEGF p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were increased in the stem cell plus exercise group (P < 0.05). These findings confirm that exercise preconditioning can potentiate the therapeutic effect of adipose-derived stem cells on cardiac remodeling in rats with myocardial infarction, and its mechanism is associated with the promotion of myocardial angiogenesis and blood perfusion.

Key words: stem cell, adipose-derived stem cell, exercise preconditioning, myocardial infarction, angiogenesis, cardiac remodeling, blood perfusion

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