粒细胞集落刺激因子联合高强度间歇运动预处理改善急性心肌梗死大鼠心脏重塑  

Granulocyte colony-stimulating factor combined with high-intensity intermittent exercise preconditioning improved cardiac remodeling in rats with acute myocardial infarction

作　　者：孙玉马[1] 马文超[1] 付常喜[1] Sun Yuma;Ma Wenchao;Fu Changxi(Department of Physical Education,Xuzhou University of Technology,Xuzhou 221008,Jiangsu Province,China)

机构地区：[1]徐州工程学院体育学院,江苏省徐州市221008

出　　处：《中国组织工程研究》2024年第31期4987-4994,共8页Chinese Journal of Tissue Engineering Research

基　　金：江苏省社会科学基金项目(22TYD001),项目负责人:付常喜。

摘　　要：背景:运动训练是多种心脏疾病的重要非药物康复手段,同时亦能够增强心脏对不良应激源(如心肌缺血)的耐受能力,即运动预处理。粒细胞集落刺激因子可有效动员干细胞归巢和分化并促进损伤心肌修复。然而两者联合作用的效果尚未明确。目的:探讨补充粒细胞集落刺激因子联合高强度间歇运动预处理对急性心肌梗死大鼠心脏重塑的影响并探讨其可能机制。方法:58只雄性Wistar大鼠按照随机数字表法分为假手术组(n=10)、模型组(n=12)、药物组(n=12)、运动组(n=12)和联合治疗组(n=12)。冠状动脉结扎法制作心肌梗死大鼠模型。运动组和联合治疗组在造模前利用电动跑台进行8周高强度间歇运动预处理,药物组和联合治疗组在造模后3 h连续5 d皮下注射人重组粒细胞集落刺激因子[10μg/(kg·d)]。给药8周后,利用超声心动术检测心脏结构与功能,取心脏进行TTC染色和Masson染色检测心肌梗死面积和胶原容积分数,免疫荧光法检测血管密度和细胞凋亡率,实时荧光定量PCR检测胚胎基因(脑钠肽、β-肌球蛋白重链)和心肌收缩调控因子(α-肌球蛋白重链、肌浆网Ca^(2+)-ATP酶)mRNA表达,Western blot法检测心脏基质细胞衍生因子1、CXC趋化因子受体蛋白4、JAK2、STAT3、Bcl-2、Bax和Cleaved-caspase-3蛋白表达。结果与结论:①与假手术组比较,模型组心肌梗死面积、胶原容积分数、细胞凋亡率增加(P<0.05);血管密度、左心室缩短分数、左心室射血分数下降(P<0.05);脑钠肽和β-肌球蛋白重链mRNA升高(P<0.05);α-肌球蛋白重链和肌浆网Ca^(2+)-ATP酶mRNA以及α-肌球蛋白重链/β-肌球蛋白重链比值下降(P<0.05);基质细胞衍生因子1、CXC趋化因子受体蛋白4、Bax、Cleaved-caspase-3蛋白表达升高(P<0.05),p-JAK2、p-STAT3、Bcl-2蛋白表达下降(P<0.05);②与模型组比较,药物组和运动组上述指标显著改善(P<0.05);与药物组和运动组比较,联�BACKGROUND:Exercise training is an important non-drug rehabilitation method for many heart diseases,and it can also enhance the heart’s tolerance to adverse stressors(such as myocardial ischemia),that is,exercise preconditioning.Granulocyte colony-stimulating factor can effectively mobilize stem cell homing and differentiation and promote the repair of damaged myocardium.However,the effect of the combination of the two treatments is not yet clear.OBJECTIVE:To explore the effect of granulocyte colony-stimulating factor supplementation combined with high-intensity intermittent exercise preconditioning on cardiac remodeling in rats with acute myocardial infarction and investigate its possible mechanism.METHODS:Totally 58 male Wistar rats were divided into sham group(n=10),model group(n=12),model drug group(n=12),model exercise group(n=12)and model combined treatment group(n=12).The myocardial infarction rat model was made by coronary artery ligation.The model exercise group and the model combined treatment group were pretreated with 8 weeks of high-intensity intermittent exercise on an electric treadmill before modeling.The model drug group and the model combined treatment group were subcutaneously injected with human recombinant granulocyte colony-stimulating factor 3 hours after modeling for 5 days(10μg/kg per day).At 8 weeks after administration,echocardiography was used to detect heart structure and function;heart was stained with 2,3,5-triphenyltetrazolium chloride and Masson staining to obtain myocardial infarct area and collagen volume fraction,respectively.Vessel density and cell apoptosis rate were detected by immunofluorescence.Real-time fluorescent quantitative PCR was utilized to detect the mRNA expression of embryonic genes(brain natriuretic peptide,β-myosin heavy chain)and myocardial contraction regulatory factors(α-myosin heavy chain,sarcoplasmic reticulum Ca^(2+)-ATPase).Western blot assay was used to detect the protein expression of cardiac stromal cell-derived factor 1,CXC chemokine receptor p

关 键 词：粒细胞集落刺激因子 高强度间歇运动 预处理 急性心肌梗死 心脏重塑 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] G804.5[文化科学—运动人体科学]