Qiliqiangxin Protects Against Cardiac Ischemia-Reperfusion Injury via Activation of the mTOR Pathway
Qiliqiangxin Protects Against Cardiac Ischemia-Reperfusion Injury via Activation of the mTOR Pathway
复制标题
七力强心通过激活 mTOR 通路预防心脏缺血再灌注损伤
DOI：
10.1159/000430368
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Li，Xinli
中科院分区：
文献类型：
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作者：
Zhou，Yonglan;Fang，Hongyi;Li，Xinli
背景/目的：芪苈强心（QL）在中国已被用于治疗慢性心力衰竭。越来越多的证据表明QL对持续性心肌缺血具有心脏保护作用。然而，尚不清楚QL是否对心脏缺血再灌注（I/R）损伤有有益作用。研究方法：结扎小鼠冠状动脉左前降支45分钟后再灌注，建立小鼠心脏I/R模型。在手术前和I/R后连续三天用QL处理小鼠。采用氯化三苯基四氮唑染色、超声心动图和Masson三色染色分别测定梗死面积、心功能和纤维化程度。Western blotting检测磷酸化mTOR（Ser 2448）、mTOR、磷酸化4 EBP（Ser 65）、4 EBP、磷酸化Akt（Ser 473）和Akt的表达水平。结果：在I/R后1天，QL治疗显著减少暴露于I/R的小鼠的梗死面积。I/R后7天，与对照组相比，QL给药组动物的死亡率降低。此外，QL处理的小鼠在I/R后1天和7天显示出增加的左心室射血分数（LVEF）和左心室缩短分数（LVFS）。与此一致，Masson三色染色证明，与对照相比，QL处理的小鼠中的间质纤维化不太明显，这表明QL处理的小鼠中的不良左心室重塑减弱。此外，蛋白质印迹分析表明，QL激活mTOR通路，而通过雷帕霉素抑制mTOR取消QL对I/R损伤的保护作用。结论：本研究表明，QL可能通过mTOR激活减弱I/R后心脏重塑的进展。这代表了QL在预防I/R损伤中的新应用。
Background/Aims: Qiliqiangxin (QL) has been used for the treatment of chronic heart failure in China. Accumulating evidence suggests QL's cardio-protective effects on continuous myocardial ischemia. However, it is unclear whether QL has beneficial effects on cardiac ischemia-reperfusion (I/R) injury. Methods: A mouse model of cardiac I/R was established by ligation of the left anterior descending coronary artery for 45 minutes followed by reperfusion. The mice were treated with QL for three days before surgery and continually after I/R. Triphenyltetrazolium chloride staining, echocardiography and Masson's trichrome staining were used to determine infarct size, cardiac function, and fibrosis, respectively. Expression levels of phospho-mTOR (Ser2448), mTOR, phospho-4EBP (Ser65), 4EBP, phospho-Akt (Ser473) and Akt were detected by Western blotting. Results: At 1 day after I/R, QL treatment significantly reduced the infarct size of mice exposed to I/R. At 7 days after I/R, mortality was reduced in QL treated animals in comparison with the control group. In addition, QL treated mice showed increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 1 and 7 days after I/R. In agreement, Masson's trichrome staining demonstrated that interstitial fibrosis was less pronounced in QL treated mice compared with controls, suggesting that adverse left ventricular remodeling is attenuated in QL treated mice. Moreover, western blotting analysis demonstrated that QL activated the mTOR pathway, while mTOR inhibition via Rapamycin abolished the protective effects of QL against I/R injury. Conclusion: This study suggests that QL attenuates the progression of cardiac remodeling after I/R likely via mTOR activation. This represents a new application for QL in the prevention of I/R injury.