桃叶珊瑚苷通过ERβ途径抑制TNF-α诱导的心脏祖细胞凋亡  

Aucubin inhibited apoptosis of mouse cardiac progenitor cells induced by TNF-α through ERβ pathway

作　　者：李春晓[1] 李慧影[1] 王虹[1] 陈璐[1] 邱丽珍[1] 耿潇[1] 尤星宇 

机构地区：[1]天津中医药大学,天津市现代中药重点实验室-省部共建国家重点实验培育基地,天津市中药药理学重点实验室,方剂学教育部重点实验室,天津300193

出　　处：《中国药理学通报》2016年第8期1068-1074,共7页Chinese Pharmacological Bulletin

基　　金：新世纪优秀人才支持计划(No NCET-13-0935);国家自然科学基金资助项目(No 81173592);国家国际科技合作专项(No 2015DFA30430);长江学者和创新团队发展计划资助项目(No IRT1276)

摘　　要：目的桃叶珊瑚苷(aucubin,AU)是杜仲、车前草、地黄等中草药的有效成分之一。现代药理学研究发现,AU对免疫、心脑血管、神经系统均有保护作用,但其作用机制尚不清楚。课题组前期研究证实AU可激活雌激素受体,提示AU可能通过雌激素信号通路发挥心血管保护作用。近年来越来越多的证据表明,心脏祖细胞(cardiac progenitor cells,CPCs)在心肌缺血组织损伤修复中发挥重要作用。方法为了进一步阐明AU的作用机制,该研究以小鼠CPCs为细胞模型,采用Incu Cyte活细胞成像、TUNEL、Western blot、定量PCR等方法探讨了AU对肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)诱导的CPCs凋亡的影响及其作用机制。结果AU可以降低由TNF-α诱导的CPCs凋亡,降低caspase-3蛋白质表达,上调Bcl-2/Bax水平,雌激素受体β(estrogen receptorβ,ERβ)抑制剂可阻断AU的抗凋亡作用,同时AU可使ERβ表达升高。结论 AU可以抑制由TNF-α诱导的CPCs凋亡,其部分作用机制为ERβ通路的激活。Aucubin（AU ） is one of the effectiveingredients of eucommia , plantain , rehmannia and otherherbs. Modern pharmacological studies have shownthat AU has protective effects on immunity , cardiovascularand nervous system , but its mechanism is unclear.Previous studies have confirmed that AU can activateestrogen receptor , suggesting that AU may play arole in cardiovascular protection through estrogen signalingpathway. In recent years , more and more evidenceshowed that cardiac progenitor cells （ CPCs ） play animportant role in the repair of myocardial ischemic injury.Methods To further elucidate the mechanism ,our study used mouse CPCs as cell model and elucidatedthe efect of AU on CPCs apoptosis induced bytumor necrosis factor alpha （TNF-α） and its mechanismby IncuCyte live cell imaging , TUNEL staining ,Western blot and quantitative PCR . Results AUcould reduce TNF-cainduced apoptosis of CPCs , decreasethe expression of caspase-3 and up-regulate Bcl-2/Bax levels. Estrogen receptor beta（ERp ） antagonistcould block the anti-apoptotic effect of AU , and AUtreatment was able to increase the expression of ERp .Conclusion AU could inhibit the apoptosis of CPCsinduced by TNF-α , and its mechanism is the activationof ERp pathway.

关 键 词：桃叶珊瑚苷 心脏祖细胞 雌激素受体p 肿瘤坏死因子-Α 细胞凋亡 组织损伤修复 

分 类 号：R-332[医药卫生] R542.2