摘要
目的探讨米诺环素后处理对大鼠心肌缺血再灌注损伤的作用及其可能机制。方法 96只雄性Wistar大鼠随机分为假手术组、缺血再灌注组、低剂量米诺环素组(3 mg/kg)和高剂量米诺环素组(10 mg/kg)。通过结扎大鼠左冠状动脉前降支45 min,再灌注2 h及24 h。再灌注2 h,检测各组心肌缺血危险区、梗死范围;血清、心肌组织TNF-α、IL-1β含量及心肌组织MPO活性;心肌凋亡指数(AI)以及心肌组织形态学改变。再灌注24 h,检测大鼠心脏血流动力学、心肌缺血危险区、梗死范围。结果与缺血再灌注组比较,低剂量、高剂量米诺环素均能降低左心室舒张末压、心肌梗死范围、AI以及血清、心肌组织TNF-α、IL-1β含量及心肌组织MPO活性,同时升高心率、左心室收缩压、±dp/dtmax(P<0.05或P<0.01)。结论米诺环素后处理能够显著抑制心肌缺血再灌注损伤诱导的大鼠心肌细胞凋亡,减少梗死范围,明显改善心功能,其机制与减少局部与系统的炎症反应有关。
Aim To investigate the effects of minocycline postconditioning on myocardial ischemia-reperfusion injury in rats and its possible mechanism. Methods Ninety-six male Wistar rats were randomly divided into four groups：sham-operation group,ischemia-reperfusion（ IR） group,low-dose minocycline（ 3 mg / kg） group and high-dose minocycline（ 10 mg/kg） group. The rat model of myocardial IR was established by occlusion of the left anterior descending coronary artery for 45 min and reperfusion for 2 hours or 24 hours. After 2 h reperfusion,myocardial area at risk and infarct size were evaluated; the amount of TNF-α,IL-1β in serum and myocardium and cardiac MPO activity were assayed; myocardial apoptosis index（ AI） and the myocardial tissue morphology were detected. The parameters of haemodynamics and myocardial area at risk and infarct size were evaluated 24 h after reperfusion. Results Compared with IR group,both low-dose and high-dose minocycline reduced LVEDP,enhanced HR,LVSP and ± dp / dtmax,lowered the amount of TNF-α,IL-1β in serum and myocardium,cardiac MPO activity,and AI（ P〈 0. 05 or P 〈0. 01）. Conclusion Minocycline postconditioning may ameliorate heart functions and decrease the infarct size and myocardial apoptosis induced by myocardial IR injury in vivo rats,and the protective effect may be related to interfering with the local and systemic inflammatory reactions.
出处
《中国动脉硬化杂志》
CAS
北大核心
2015年第9期870-875,共6页
Chinese Journal of Arteriosclerosis
基金
辽宁省教育厅科学研究一般项目(L2013399)
沈阳医学院博士科研启动基金项目(20133050)
关键词
米诺环素
缺血后处理
心肌缺血再灌注损伤
Minocycline
Ischemia Postconditioning
Myocardial Ischemia-reperfusion Injury
