Wang Ruiying, Yang Minghua, Wang Min, Liu Xuesong, Xu Huibo, Xu Xudong, Sun Guibo, Sun Xiaobo
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Harbin University of Commerce, Harbin, China.
Cell Physiol Biochem. 2018;50(1):28-40. doi: 10.1159/000493954. Epub 2018 Oct 2.
BACKGROUND/AIMS: Total saponins of Aralia elata (Miq) Seem (AS) from the Chinese traditional herb Long ya Aralia chinensis L. reportedly provide cardioprotective effects, but the exact mechanisms require further study. Previous studies have showed that myocardial ischemia/ reperfusion injury (MIRI) was related to calcium homeostasis imbalance and endoplasmic reticulum stress (ERS). Thus, this study aimed to demonstrate protective effects of AS on MIRI.
After administrating AS for 5 days, the left anterior descending artery coronary artery of Sprague-Dawley (SD) rats was ligated for 30 min. After 48 h of reperfusion, haemodynamics, Evans blue/ 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, masson staining and the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA) were detected to assess MIRI. ATPase activity and Western Blot were used to study the mechanisms.
Compared with IR group, AS treatment groups could significantly reduce myocardial infarct size; improve myocardial pathologic progress; decrease content of LDH, CK, and MDA; increase content of SOD; and restore the activities of Ca2+-Mg2+-ATPase, Na+-K+-ATPase, sarcoplasmic reticulum Ca2+-ATPases (SERCA), and calcineurin (CaN). AS treatment groups also significantly up-regulated the expression of GRP78, C/EBP homologous protein (CHOP), and Bax, and down-regulated the expression of Bcl-2, all similar to the effects of ERS.
These findings illustrated that AS could prevent myocardial ischemia/reperfusion injury and reduce calcium homeostasis imbalance and ERS-related apoptosis.
背景/目的:据报道,传统中药龙牙楤木中的辽东楤木总皂苷(AS)具有心脏保护作用,但其确切机制仍需进一步研究。先前的研究表明,心肌缺血/再灌注损伤(MIRI)与钙稳态失衡和内质网应激(ERS)有关。因此,本研究旨在证明AS对MIRI的保护作用。
连续5天给予AS后,结扎Sprague-Dawley(SD)大鼠的左冠状动脉前降支30分钟。再灌注48小时后,检测血流动力学、伊文思蓝/氯化三苯基四氮唑(TTC)染色、苏木精-伊红(HE)染色、Masson染色以及乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平,以评估MIRI。采用ATP酶活性检测和蛋白质免疫印迹法研究其机制。
与缺血/再灌注(IR)组相比,AS治疗组可显著减小心肌梗死面积;改善心肌病理进程;降低LDH、CK和MDA含量;增加SOD含量;恢复Ca2+-Mg2+-ATP酶、Na+-K+-ATP酶、肌浆网Ca2+-ATP酶(SERCA)和钙调神经磷酸酶(CaN)的活性。AS治疗组还显著上调葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)和Bax的表达,下调Bcl-2的表达,这些变化均与ERS的作用相似。
这些研究结果表明,AS可预防心肌缺血/再灌注损伤,减少钙稳态失衡和ERS相关的细胞凋亡。