运动预处理联合骨髓间充质干细胞移植治疗大鼠心肌梗死  

Exercise preconditioning combined with bone marrow mesenchymal stem cell transplantation for myocardial infarction in rats

作　　者：王治坤 白少玄 赵伟[2] 王晨宇[1] Wang Zhikun;Bai Shaoxuan;Zhao Wei;Wang Chenyu(Zhengzhou University of Aeronautics,Zhengzhou 450015,Henan Province,China;Logistics University of Chinese People’s Armed Police Forces,Tianjin 300309,China)

机构地区：[1]郑州航空工业管理学院,河南省郑州市450015 [2]中国人民武装警察部队后勤学院,天津市300309

出　　处：《中国组织工程研究》2025年第1期65-73,共9页Chinese Journal of Tissue Engineering Research

基　　金：河南省科技攻关项目(232102321125),项目负责人:王晨宇。

摘　　要：背景:干细胞疗法在改善心肌梗死后心脏重构方面具有广阔前景,但心肌微环境改变影响干细胞疗效。运动预处理类似于缺血预处理,能够对心肌产生保护作用。然而,运动预处理与干细胞移植联合作用的效果与机制鲜有关注。目的:观察运动预处理对心肌梗死大鼠骨髓间充质干细胞移植效果的影响,探讨局部炎症微环境在其中的作用机制。方法:80只雌性SD大鼠随机分为假手术组、模型组、移植组和联合组,每组20只。利用结扎冠状动脉左前降支的方法制作心肌梗死大鼠模型,假手术组仅穿线不结扎。移植组和联合组造模后于心肌内注射雄性大鼠来源骨髓间充质干细胞,此外,联合组在造模前还需进行8周跑台运动(即运动预处理)。干细胞移植后4周,采用递增负荷运动力竭实验测定运动能力,超声心动术测定心脏结构与功能,压力容积导管法检测左心室血液动力学,原位染色法进行心肌组织病理学观察并获取心肌胶原容积分数。干细胞移植后1,7 d和4周,采用定量反转录聚合酶链反应检测左心室促炎症因子(白细胞介素1β、白细胞介素6、肿瘤坏死因子α)、抗炎症因子(白细胞介素10)、Y染色体性别决定区和胚胎基因(心房钠尿肽、脑钠肽、β-肌球蛋白重链)m RNA表达量。结果与结论:(1)干细胞移植后4周:与假手术组比较,模型组运动能力、左心室射血分数降低(P <0.05);心肌梗死面积、心肌细胞横截面积、胶原容积分数增加(P <0.05);胚胎基因以及促炎因子m RNA表达量上调(P <0.05),白细胞介素10 m RNA表达量下调(P <0.05)。与模型组比较,移植组运动能力、左心室射血分数增加(P <0.05);心肌梗死面积、心肌细胞横截面积、胶原容积分数下降(P <0.05);胚胎基因以及促炎因子m RNA表达量下调(P <0.05),白细胞介素10 m RNA表达量无显著性变化(P> 0.05)。与移植组比较,联合组上述各指标均进一步�BACKGROUND:Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction;however,alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells.Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium.However,little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation.OBJECTIVE:To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment.METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group,and combination group,with 20 rats in each group.The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery.The sham operation group was only threaded without ligature.The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling.In addition,the combination group also required 8 weeks of treadmill exercise(i.e.,exercise preconditioning) before modeling.Four weeks after stem cell transplantation,exercise performance was measured by incremental exercise exhaustion test;cardiac structure and function were measured by echocardiography;left ventricular hemodynamics was measured by pressure-volume catheterization,and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained.Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor(interleukin-1β,interleukin-6,tumor necrosis factor-α),anti-inflammatory factor(interleukin-10),sexdetermining region of Y chromosome,and fetal genes(atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain) mRNA expression level at 1

关 键 词：运动预处理 心肌梗死 骨髓间充质干细胞 心脏重构 炎症反应 微环境 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学] R542.2