Cheng Wenkun, Wang Lei, Yang Tao, Wu Aiming, Wang Baofu, Li Tong, Lu Ziwen, Yang Jingjing, Li Yang, Jiang Yangyang, Wu Xiaoxiao, Meng Hui, Zhao Mingjing
Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Physiol. 2020 Jul 17;11:805. doi: 10.3389/fphys.2020.00805. eCollection 2020.
Metabolic modulation is a promising therapy for ischemic heart disease and heart failure. This study aimed to clarify the regional modulatory effect of Qiliqiangxin capsules (QLQX), a traditional Chinese medicine, on cardiac metabolic phenotypes. Sprague-Dawley rats underwent left anterior descending coronary artery ligation and were treated with QLQX and enalapril. Striking global left ventricular dysfunction and left ventricular remodeling were significantly improved by QLQX. In addition to the posterior wall, QLQX also had a unique beneficial effect on the anterior wall subject to a severe oxygen deficit. Cardiac tissues in the border and remote areas were separated for detection. QLQX enhanced the cardiac F-fluorodeoxyglucose uptake and the levels and translocation of glucose transport 4 (GLUT4) in the border area. Meanwhile, it also suppressed glucose transport 1 (GLUT1) in both areas, indicating that QLQX encouraged border myocytes to use more glucose in a GLUT4-dependent manner. It was inferred that QLQX promoted a shift from glucose oxidation to anaerobic glycolysis in the border area by the augmentation of phosphorylated pyruvate dehydrogenase, pyruvate dehydrogenase kinases 4, and lactic dehydrogenase A. QLQX also upregulated the protein expression of fatty acid translocase and carnitine palmitoyl transferase-1 in the remote area to possibly normalize fatty acid (FA) uptake and oxidation similar to that in healthy hearts. QLQX protected global viable cardiomyocytes and promoted metabolic flexibility by modulating metabolic proteins regionally, indicating its potential for driving the border myocardium into an anaerobic glycolytic pathway against hypoxia injuries and urging the remote myocardium to oxidize FA to maximize energy production.
代谢调节是一种有前景的治疗缺血性心脏病和心力衰竭的方法。本研究旨在阐明中药芪苈强心胶囊(QLQX)对心脏代谢表型的区域调节作用。将Sprague-Dawley大鼠进行左前降支冠状动脉结扎,并给予QLQX和依那普利治疗。QLQX显著改善了明显的整体左心室功能障碍和左心室重塑。除后壁外,QLQX对严重缺氧的前壁也有独特的有益作用。分离梗死周边和远隔区域的心脏组织进行检测。QLQX增强了梗死周边区域心脏的F-氟脱氧葡萄糖摄取以及葡萄糖转运蛋白4(GLUT4)的水平和转位。同时,它也抑制了两个区域的葡萄糖转运蛋白1(GLUT1),表明QLQX促使梗死周边心肌细胞以依赖GLUT4的方式使用更多葡萄糖。据推测,QLQX通过增强磷酸化丙酮酸脱氢酶、丙酮酸脱氢酶激酶4和乳酸脱氢酶A,促进梗死周边区域从葡萄糖氧化向无氧糖酵解转变。QLQX还上调了远隔区域脂肪酸转位酶和肉碱棕榈酰转移酶-1的蛋白表达,可能使脂肪酸(FA)摄取和氧化正常化,类似于健康心脏。QLQX通过区域调节代谢蛋白保护整体存活心肌细胞并促进代谢灵活性,表明其有潜力促使梗死周边心肌进入无氧糖酵解途径以对抗缺氧损伤,并促使远隔心肌氧化FA以最大化能量产生。