脑源性神经营养因子预处理减轻大鼠心肌缺血再灌注损伤  

Effect of Brain-derived Neurotrophic Factor Pretreatment for Reducing Myocardial Ischemia/reperfusion Injury in Experimental Rats

作　　者：吕明义[1] 邓淑玲[1] 龙晓凤[1] 

机构地区：[1]大连大学附属中山医院内科ICU,辽宁省大连市116000

出　　处：《中国循环杂志》2016年第2期175-179,共5页Chinese Circulation Journal

摘　　要：目的:研究经脑源性神经营养因子(BDNF)预处理后对大鼠心肌缺血再灌注损伤(I/R)的影响及其作用机制。方法:将50只SD大鼠通过结扎左前降支、心肌缺血30 min后再灌注180 min,建立心肌I/R模型,并分为5组,(每组10只),即假手术组、心肌缺血再灌注组(单独I/R组)、以3个不同浓度即1、10、100 nmol/(kg·ml)的BDNF行预处理后的心肌I/R分为3个组即心肌I/R 1组、心肌I/R 2组和心肌I/R 3组。在I/R结束后,记录血液动力学指标左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室内压最大上升速率和下降速率(±dp/dt max);检测各组大鼠血清中乳酸脱氢酶(LDH)、肌酸激酶和心肌组织中丙二醛(MDA)、超氧化物歧化酶(SOD)活性;利用依文思蓝染色法测定各组大鼠左心室心肌梗死面积比;原位缺口末端标记法(Tunel)染色检测各组大鼠心肌组织凋亡细胞;蛋白免疫印迹(Western-blot)方法检测各组大鼠心肌组织中总酪氨酸激酶受体B(Total-Trk B)和磷酸化酪氨酸激酶受体B(p-Trk B)水平。结果:与单独I/R组相比,心肌I/R 3个组中大鼠的LVSP、±dp/dt max均逐渐回升,而LVEDP逐渐下降;LDH、肌酸激酶漏出量和MDA含量逐渐下降,而SOD活性逐渐回升;心肌梗死面积占缺血危险区面积比由(47.54±6.35)%逐渐下降至(28.68±4.56)%;心肌细胞凋亡率由(37.89±5.46)%逐渐下降至(10.24±3.05)%,p-Trk B/Total-Trk B水平也随之由(0.16±0.03)逐渐上升至(0.42±0.03)。上述比较差异均有统计学意义(P<0.05)。结论:BDNF预处理能够维持大鼠心肌I/R损伤后的心肌状态及功能,减少心肌梗死面积,降低其受氧化损伤和细胞凋亡,并通过激活Trk B受体磷酸化发挥作用,表明BDNF预处理能够保护心肌细胞减轻其I/R损伤。Objective： To investigate the effect and mechanism of brain-derived neurotrophic factor （BDNF） pretreatment for reducing myocardial ischemia/reperfusion （I/R） injury in experiment rats. Methods： Rat＇s myocardial UR model was established by left anterior descending artery ligation for 30min followed-by reperfusion for 180 min. The rats were divided into 5 groups： Sham operation group, I/R group and IR with BDNF pretreatment （1, 10, 100） nmol/（kg, ml） groups respectively. The LVSP, LVEDP, ±dp/dlmax were recorded after I/R; serum levels ofLDH, CK and the cardiac tissue levels of MDA, SOD were examined; the ratios of left ventricular myocardial infarction area in different groups were observed by by Evans blue staining; cell apoptosis rates were evaluated by Tunel staining; the total-TrkB and p-TrkB in myocardium were detected by Western-blot analysis. Result： Compared with I/R group, in 3 IR with BDNF pretreatment groups, LVSP, ±dp/dtmax were gradually increasing and LVEDP were gradually decreasing, all P〈0.05; the leaking levels of LDH, CK and the content of MDA were gradually decreeing and the SOD activity was gradually increasing, all P〈0.05; the average ratios ofMI area/ischemic area were decreased from （47.54 ± 6.35） % to （28.68 ± 4.56） %, the apoptosis rates decreased from （37.89 ±5.46） % to （10.24 ± 3.05） %, the level of p-trkB/Total-TrkB increased from （0.16±0.03） to （0.42 ±0.03）, P〈0.05. Conclusion： BDNF pretreatment could maintain the cardiac function in experiment rats after I/R injury, it may reduce MI area, decrease oxidative damage and apoptosis, therefore, protect myocardial cells for reducing IR injury.

关 键 词：神经营养因子 心肌再灌注损伤 缺血预处理 

分 类 号：R541[医药卫生—心血管疾病]