热休克蛋白A12B对缺血/再灌注损伤心肌微血管内皮完整性的保护作用  

Protective effects of heat shock protein A12B on myocardial microvascular endothelial integrity after ischemia/reperfusion injury in mice

作　　者：李楠[1] 孔秋月[1] 戴乐杨 丁正年[1] LI Nan, KONG Qiu-yue, DAI Le-yang, DING Zheng-nian.(Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Chin)

机构地区：[1]南京医科大学第一附属医院麻醉科,江苏省南京市210029

出　　处：《实用老年医学》2018年第7期613-615,共3页Practical Geriatrics

摘　　要：目的探讨热休克蛋白A12B(heat shock protein A12B,HSPA12B)对心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤后微血管无复流现象、血管通透性及其微血管内皮结构完整性的影响。方法实验选用同窝、8~10周龄雄性HSPA12B转基因鼠(HSPA12B Transgenic,Tg)和野生型鼠(wild type,WT)。所有小鼠均接受手术,即结扎冠状动脉左前降支诱导心肌缺血(45 min),松开结扎为I/R开始。I/R 30 min后,采用番茄血凝素免疫荧光标记检测心肌微血管血流灌注情况,伊文斯兰染料检测心肌微血管渗透性。I/R 4 h后取小鼠心脏组织,电子显微镜观察心肌微血管内皮细胞超微结构变化。结果 I/R损伤后,与WT鼠相比,Tg鼠心肌无复流面积显著减少,血管通透性明显降低,微血管内皮细胞损伤减少且细胞间连接更加完整。结论高表达HSPA12B显著减轻心肌I/R诱导的心肌微血管内皮细胞结构和功能损伤,从而保护心肌I/R损害,提示HSPA12B可能为治疗心肌I/R损伤的新靶点。Objective To investigate the effects of heat shock protein A12B（HSPA12B） on microvascular no-reflow phenomenon,vascular permeability,microvascular endothelial structural integrity after myocardial ischemia/reperfusion（I/R） injury in mice. Methods Male littermates of transgenic mice（Tg） with overexpression of HSPA12B and wild type（WT） mice aged 8-10 weeks were enrolled in the experiments. The mice received the intervention that left anterior descending（LAD） coronary artery was ligated for ischemia（45 min） and then loosened for reperfusion. The myocardial microvascular reflow was detected using FITC-labeled Lycopersicon esculentum（Tomato） lectin and vascular leakage in myocardium was measured by Evan＇s blue extravasation 30 min after myocardial I/R. Ventricular tissues were collected 4 h after I/R and ultrastructural of myocardial microvascular endothelial cells（EC） were observed by using a transmission electron microscope. Results Compared with WT mice,the no-reflow area decreased,the vascular permeability decreased,the intact of EC-EC tight junction increased and the ECs damages decreased significantly in HSPA12B Tg mice after myocardial I/R injury. Conclusions Overexpression of HSPA12 B can significantly attenuate myocardial I/R injury via maintaining the structure and function integrity of myocardial microvascular EC,suggesting that targeting endothelial HSPA12B may provide a new strategy for the treatment of myocardial I/R injury in patients.

关 键 词：热休克蛋白A12B 心肌缺血/再灌注损伤 微血管内皮细胞 

分 类 号：R541[医药卫生—心血管疾病]