跑台运动预干预通过抑制心肌炎症因子和凋亡改善心肌缺血/再灌注大鼠心肌损伤及心功能

Treadmill Exercise Pre-intervention Improved Myocardial Injury and Cardiac function by Inhibiting Inflammatory Factors and Apoptosis in Rats with Myocardial Ischemia/Reperfusion

目的:探讨8周跑台运动预干预对心肌缺血再灌注(myocardial ischemia reperfusion injury,MI/R)大鼠心肌组织及心脏功能的影响,并通过检测心肌组织炎症因子(肿瘤坏死因子-α,TNF-α;白介素-6,IL-6;白介素-10,IL-10)和凋亡蛋白半胱天冬酶(capase-3)的表达,探讨跑台运动预干预影响MI/R大鼠心肌损伤及心脏功能的可能机制。方法:将48只雄性成年SD大鼠随机分为3组,假手术组(sham group)、心肌缺血再灌注组(MI/R group)及运动预干预+心肌缺血再灌注组(MI/R+EX group),随后MI/R+EX组大鼠进行8周中等强度跑台运动预干预。运动结束后通过结扎左冠脉动脉前降支缺血30 min,再灌注120 min建立MI/R模型,用BL-420S生物机能实验系统监测大鼠3个时间点(缺血前、缺血30 min、再灌注120 min)左室收缩压(LVSP)、左室舒张末期压(LVDEP)及左室内压上升及下降的最大变化速率(±dp/dt max),于再灌注结束后HE染色检测各组心肌病理学改变情况,伊文思蓝和2,3,5-氯化三苯基四氮唑蓝双重染色法测定心肌梗死面积;以ELISA和免疫组织化学法分别检测心肌组织TNF-α、IL-6及IL-10水平和心肌组织capase-3的表达。结果:(1)与sham组比较,MI/R组大鼠心肌组织呈明显病理改变,梗死区面积/缺血期面积显著增加,左室收缩压(LVSP)、左室内压上升及下降最大速率(±dp/dt max)均显著下降,左室舒张末期压力(LVDEP)显著增加(P均<0.01);心肌组织TNF-α及IL-6水平明显增加,IL-10水平明显下降,capase-3平均光密度(MOD)增加(P<0.01)。(2)8周跑台运动预干预可显著改善MI/R大鼠的心肌组织病理变化及心脏舒缩功能,减少心肌梗死面积,心肌组织TNF-α及IL-6水平明显下降,IL-10水平明显增加,capase-3 MOD降低(P<0.01,P<0.05)。结论:跑台运动预干预对心肌缺血再灌注心肌损伤具有保护作用,其机制可能与此运动平衡MI/R大鼠促炎和抗炎细胞因子,降低caspase-3表达,从而抑制细胞凋亡有关。

Objective:To explore the possible mechanism of 8-week treadmill exercise pre-intervention on myocardial injury and cardiac function by detecting inflammatory cytokine and capase-3 expression in cardiac muscle tissue.Methods:48 SD rats were randomly allocated into three groups(n=16):sham group,myocardial ischemia-reperfusion group(MI/R group)and MI/R+EX group.Then,the rats in EX+MI/R groups were conducted middle intensity treadmill exercise for 8 weeks.After exercise,the left anterior descending coronary artery was ligated for 30 min and then reperfused for 120 min to establish the MI/R model.The values of left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVDEP)and±dp/dtmax were measured by BL-420s biological function test system at pre-ischemia,ischemia 30 min and 120 min of reperfusion.After reperfusion,HE staining was used to detect the changes of myocardial pathology and myocardial infarction size was measured by using Evans blue and tetrazolium chloride double staining.The capase-3 expression and levels of TNF-α,IL-6 and IL-10 were detected by immunohistochemistry and ELISA.Results:(1)Compared with the sham group,the cardiac muscle tissue showed obvious pathological changes and myocardial infarction size/risk area of ischemia significantly increased(P<0.01);LVSP and±dp/dtmax significantly decreased,LVDEP significantly increased(P<0.01);the levels of TNF-α,IL-6 and mean optical density(MOD)of capase-3 significantly increased,IL-10 level decreased(P<0.01 respectively)in MI/R group rats.(2)Treatment of I/R rats with exercise preconditioning improved MI/R induced the morphological changes in myocardial fiber and cardiac function,myocardial infarction size/risk area of ischemia significantly decreased(P<0.01);the levels of TNF-α,IL-6 and MOD of capase-3 significantly decreased,IL-10 level increased(P<0.01)in MI/R+EX group rats when compared with the MI/R group rats.Conclusion:Exercise preconditioning has a protective effect on myocardial ischemia-reperfusion injury,which may be related to the balance of pro-inflammatory and anti-inflammatory cytokines and the reduction of caspase-3 expression and inhibition of apoptosis.