Yu Qian, Li Xin, Cao Xia
Department of Pharmacy, Jilin University, Changchun, China; Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun, China.
Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun, China.
Ann Vasc Surg. 2016 Jul;34:234-42. doi: 10.1016/j.avsg.2016.04.002. Epub 2016 Apr 27.
The aim of the study was to examine and confirm the cardioprotective effect and mechanism of phenylethanoid glycoside-rich extract of Cistanche deserticola (PhG-RE), a well-known natural antioxidant-based active constituents, against ischemia/reperfusion injury using both in vivo and in vitro approaches.
A total of 30 Sprague-Dawley rats were divided in to 3 groups as group 1: sham laparotomy, group 2: IR, and group 3: IR + PhG-RE group (0.25 mg/mL/min). Hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. The myocardial infarct size and the activities of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) were measured. Myocardial tissue malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were detected. Western blot analysis was carried out to determine the cardioprotective mechanisms of PhG-RE.
Hearts treated with PhG-RE showed a significant reduction in infarct size and decrease in CK-MB and LDH activities. PhG-RE also reduced MDA levels and elevated the activities of GSH-Px, SOD. The expressions of cytochrome-c were significantly reduced in the treated group. A significant upregulation of antiapoptotic proteins Bcl-2/Bax with simultaneous downregulation of cleaved-caspase-3 was observed. The molecular signaling cascade, including phospho-Akt (ser-473) and phospho-GSK3β that lead to the activation or suppression of apoptotic pathway, also showed a significant protective role in the treatment group.
The results suggested that the PhG-RE may reduce the oxidative stress in the reperfused myocardium and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection.
本研究旨在通过体内和体外实验方法，研究并证实富含苯乙醇苷的肉苁蓉提取物（PhG-RE）——一种以天然抗氧化剂为基础的活性成分，对缺血/再灌注损伤的心脏保护作用及其机制。
将30只Sprague-Dawley大鼠分为3组：第1组为假手术组，第2组为缺血/再灌注组（IR），第3组为缺血/再灌注+PhG-RE组（0.25mg/mL/min）。心脏先进行30分钟的全心缺血，然后再灌注45分钟。测量心肌梗死面积以及肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）的活性。检测心肌组织丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）水平。采用蛋白质免疫印迹分析来确定PhG-RE的心脏保护机制。
用PhG-RE处理的心脏梗死面积显著减小，CK-MB和LDH活性降低。PhG-RE还降低了MDA水平，提高了GSH-Px和SOD的活性。治疗组细胞色素c的表达显著降低。观察到抗凋亡蛋白Bcl-2/Bax显著上调，同时裂解的半胱天冬酶-3下调。包括磷酸化Akt（ser-473）和磷酸化GSK3β在内的分子信号级联反应，可导致凋亡途径的激活或抑制，在治疗组中也显示出显著的保护作用。
结果表明，PhG-RE可能减轻再灌注心肌中的氧化应激，并在抑制导致心脏保护的凋亡途径中发挥重要作用。
