γ-分泌酶抑制剂对姜黄素后处理心肌保护作用的影响  

Effects of curcumin post-treatment against myocardial ischemia and reperfusion by activation of the Notch signaling pathway

作　　者：王宁[1] 段维勋[1] 杨阳[1] 李悦[2] 梁振兴[1] 金振晓[1] 易定华[1] 俞世强[1] 

机构地区：[1]第四军医大学西京医院,西安710032 [2]第四军医大学口腔医学系

出　　处：《山东医药》2013年第6期4-8,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81070198);陕西省社会发展推动基金资助项目(2012JQ4001)

摘　　要：目的探讨Notch信号通路在姜黄素(Cur)后处理抗心肌缺血再灌注损伤(IR)中的作用。方法将40只SD大鼠随机分为对照组、IR组、Cur组、Cur+DAPT组、DAPT组各8只。各组均采用离体心脏Langendoff逆行灌注10 min致心肌缺血,停止灌注80 min后除对照组外其余各组均予KH液行再灌注至150 min。Cur组再灌注液中含1μM浓度的Cur,Cur+DAPT组含1μM浓度的Cur和0.5μM浓度的DAPT;DAPT组含0.5μM浓度的DAPT。监测各组缺血前及再灌注后血流动力学指标,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);氯化三苯基四氮唑(TTC)染色法测定心肌梗死(MI)面积;专用试剂盒测定冠脉流出液(CF)中乳酸脱氢酶水平(LDH);Western blot法检测心肌组织Notch1表达。结果与对照组比较,IR组再灌注后各时间点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LDH含量显著升高(P<0.01),Notch1表达下降(P<0.01);与IR组比较,Cur组上述指标显著改善(P<0.01),Notch1表达上升(P<0.01);与Cur组比较,Cur+DAPT组上述指标显著恶化,且Notch1表达下降(P<0.01);与IR组比较,DAPT组各项指标差异无统计学意义。结论 Cur后处理对大鼠心肌缺血再灌注损伤有保护作用,其作用机制可能与活化Notch信号通路有关。Objective To investigate the role of Notch signaling pathway in the protective effects of Cur post-treatment after myocardial ischemia reperfusion injury （IRI）. Methods The isolated hearts of SD rats were perfused with Lange- ndroff and then were divided into 5 groups： control group, I/RI group, I/RI ＋ Cur（ 1 μM） group, I/RI ＋ Cur（ 1 μM） ＋ DAPT（0.5 μM） group, L/RI ＋ DAPT（0.5 μM） group. Myocardial injuries in the rat hearts were produced by ischemia for 90 rain and followed by 60 rain reperfusion. HR, LVDP, ＋ dp/dt max, and CF were recorded respectively before ische- mia and 15, 30, 45 and 60 rain after reperfusion. The myocardial infarct size （MI） was detected by TI＇C test. Special kits were used to detected the levels of lactic dehydrogenase （LDH） in the coronary flow （CF）. Western blot was used to de- tect the expression of Notchl. Results Compared with control group, the systolic and diastolic functions in the I/RI group reduced （ P 〈 0.01 ）, the MI and LDH in the CF increased （ P 〈 0.01 ）, the expression of Notch1 decreased （ P 〈 0.01 ）. Compared with the I/RI group, the above parameters in the I/RI ＋ Cur group were improved （P 〈 0.01 ） and the expres- sion of Notchl increased （P 〈 0.01 ）. Compared with the I/RI ＋ Cur group, the above parameters in the I/RI ＋ Cur ＋ DAPT group worsened （P 〈0：01 ）, the expression of Notch1 decreased （P 〈0.01 ）. Compared with the I/RI group, the parameters in the I/RI ＋ DAPT group had no significant difference （P 〉 0.05） and the expression of Notch1 decreased sig-nificantly （P 〈 O. O1 ）. Conclusion Post-treatment with Cur can significantly reduce myocardial ischemia-reperfusion inju- ry, which is closely related to the activation of Notch signaling pathway.

关 键 词：心肌缺血再灌注损伤 姜黄素 后处理 DAPT NOTCH信号通路 

分 类 号：R541[医药卫生—心血管疾病]