γ-分泌酶抑制剂对大鼠离体心脏缺血再灌注损伤的作用  

Effects of γ-secretase inhibitor on isolated rat heart induced by ischemia reperfusion injury

作　　者：杨阳[1] 段维勋[1] 王宁[1] 梁振兴[1] 姜鹏[2] 周建[3] 金振晓[1] 易定华[1] 

机构地区：[1]第四军医大学西京医院心血管外科,西安710032 [2]中国人民解放军第82医院骨科,淮安223100 [3]中国人民解放军第253医院口腔科,呼和浩特010010

出　　处：《中国体外循环杂志》2013年第1期41-44,共4页Chinese Journal of Extracorporeal Circulation

基　　金：国家自然科学基金资助(81070198;81102687);陕西省社会发展推动基金资助(2012JQ4001;2012SF2-21-1)

摘　　要：目的γ-分泌酶抑制剂(DAPT)是Notch信号通路特异性阻断剂,本实验将研究DAPT对SD大鼠离体心脏缺血再灌注损伤(I/RI)的影响,为探明Notch信号通路在心肌I/RI中的作用提供理论依据。方法采用离体大鼠心脏Langendorff逆行灌注模型,缺血50 min,再灌注60 min。实验分为4组,分别为正常对照组(Control)、I/RI组、DAPT(1μM)+I/RI组,DAPT(1μM)组。监测缺血前后血流动力学各项指标,包括:心率(HR)、左心室发展压(LVDP)、左心室内压最大变化速率(+dp/dtmax)、冠脉流量(CF)、计算出心率压力指数(DP,LVDP×HR/1000);氯化三苯基四氮唑(TTC)染色法测定各组心肌梗死(MI)的面积;专用试剂盒测定冠脉流出液(CF)中乳酸脱氢酶含量(LDH)。结果与Control组比较,I/R组缺血后各时间点的收缩及舒张功能均显著降低(P<0.01),MI面积显著增加(P<0.01),冠脉流出液中LDH含量显著升高(P<0.01);与I/RI组比较,DAPT+I/RI组可以加重上述指标进一步恶化(P<0.01);与Control组比较,DAPT各项指标无统计学差异(P>0.05)。结论DAPT有加重心肌缺血再灌注损伤的作用,Notch信号通路可能在心肌缺血再灌注损伤中发挥重要的调控作用。Objective DAPT is a specific inhibitor of Notch signaling pathway, our study investigated the effects of DAPT on isolated rat hearts induced by ischemia reperfusion injury （I/RI）, and to explore the role of Notch signaling pathway in myocardial ischemia reperfusion injury （I/RI）. Methods The hearts of SD rats were isolated, underwent Langendroff perfusion, and were divided into 4 groups： Control, I/RI, DAPT （1 μM） ＋I/RI, DAPT （1 μM）. Myocardial injuries in the rat hearts were produced by ischemia for 50 min and followed by 60 min reperfusian. HR, LVDP, ± dp/dt max, CF and DP were recorded respectively before ischemia and 15, 30, 45 and 60 min after reperfusion; the myocardial infarct size （MI） was detected by TTC test; the special kits were used to detect the levels of lactic dehydrogenase （LDH） in the coronary flow （CF）. Results In the I/R group, the systolic and diastolic functions significantly reduced （ P 〈 0.01 ）, the MI and LDH in the CF increased significantly （ P 〈 0.01 ）. Compared to the I/RI group, the above parameters in DAPT ＋ IR group were worse （ P 〈 0.01 ） ; compared to the Control group, the parameters in DAPT group had no significant difference （ P 〉 0.05）. Conclusion DAPT can aggravate the myocardial I/RI, Notch signaling pathway may play a vital regulatory role in the myocardial reperfusion injury.

关 键 词：Γ-分泌酶抑制剂 离体大鼠心脏 缺血再灌注损伤 心肌保护 

分 类 号：R654.2[医药卫生—外科学]