Li Qing, Li Na, Cui He-He, Tian Xia-Qiu, Jin Chen, Chen Gui-Hao, Yang Yue-Jin
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.
Exp Physiol. 2017 Apr 1;102(4):422-435. doi: 10.1113/EP086192. Epub 2017 Mar 14.
What is the central question of this study? In a rat model of acute myocardial infarction (AMI), we investigated the effect of Tongxinluo (TXL) treatment. Does TXL activate autophagy and attenuate apoptosis of cardiomyocytes through the AMPK pathway to facilitate survival of cardiomyocytes and improve cardiac function? What is the main finding and its importance? Major findings are as follows: (i) TXL treatment preserved cardiac function and reduced ventricular remodelling, infarct size and inflammation in rat hearts after AMI; (ii) TXL treatment dramatically increased autophagy and inhibited apoptosis in myocardium; and (iii) the AMPK signalling pathway played a crucial role in mediating the beneficial effects of TXL. Tongxinluo (TXL) has been demonstrated to have a protective role during ischaemia-reperfusion after acute myocardial infarction, but the long-term effects and underlying mechanisms are still unknown. The aim of this study was to investigate whether TXL could have an effect on apoptosis or autophagy of cardiomyocytes through the AMP-activated protein kinase (AMPK) pathway. Male Sprague-Dawley rats (n = 75) were randomly divided to sham, control, TXL (4 mg kg day orally), compound C (i.p. injection of 10 mg kg day ) and TXL + compound C groups. The extent of fibrosis, infarct size and angiogenesis were determined by pathological and histological studies. Four weeks after acute myocardial infarction, TXL treatment significantly increased ejection fraction, promoted angiogenesis in the peri-infarct region and substantially decreased fibrosis and the size of the infarcted area (P < 0.05). Treatment with TXL also increased AMPK/mTOR phosphorylation, upregulated expression of the autophagic protein LC3 and downregulated expression of the apoptotic protein Bax in the infarcted myocardium (P < 0.05). Addition of the AMPK inhibitor, compound C, counteracted these beneficial effects significantly (P < 0.05). The cardioprotective benefits of TXL against myocardial infarction are related to the inhibition of apoptosis and promotion of autophagy in rat hearts after acute myocardial infarction. This effect may occur through the AMPK signalling pathway.
本研究的核心问题是什么？在急性心肌梗死（AMI）大鼠模型中，我们研究了通心络（TXL）治疗的效果。通心络是否通过AMPK途径激活自噬并减轻心肌细胞凋亡，从而促进心肌细胞存活并改善心脏功能？主要发现及其重要性是什么？主要发现如下：（i）通心络治疗可保留心脏功能，并减少AMI后大鼠心脏的心室重构、梗死面积和炎症；（ii）通心络治疗可显著增加心肌自噬并抑制凋亡；（iii）AMPK信号通路在介导通心络的有益作用中起关键作用。通心络已被证明在急性心肌梗死后的缺血再灌注过程中具有保护作用，但其长期影响和潜在机制仍不清楚。本研究的目的是探讨通心络是否能通过AMP激活蛋白激酶（AMPK）途径对心肌细胞凋亡或自噬产生影响。将雄性Sprague-Dawley大鼠（n = 75）随机分为假手术组、对照组、通心络组（口服4 mg·kg⁻¹·d⁻¹）、复合C组（腹腔注射10 mg·kg⁻¹·d⁻¹）和通心络+复合C组。通过病理和组织学研究确定纤维化程度、梗死面积和血管生成情况。急性心肌梗死后四周，通心络治疗显著增加射血分数，促进梗死周边区域血管生成，并显著减少纤维化和梗死面积大小（P < 0.05）。通心络治疗还增加了梗死心肌中AMPK/mTOR磷酸化水平，上调自噬蛋白LC3的表达，并下调凋亡蛋白Bax的表达（P < 0.05）。添加AMPK抑制剂复合C可显著抵消这些有益作用（P < 0.05）。通心络对心肌梗死的心脏保护作用与急性心肌梗死后大鼠心脏中凋亡的抑制和自噬的促进有关。这种作用可能通过AMPK信号通路发生。
