桃叶珊瑚苷(acbm,AU)是杜仲、车前草、地黄等中草药的有效成分之-.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(cardiacprogenitorcells,CPC/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IncuCyte活细胞成像、TUNEUWesternblot、定量PCR等方法探讨了AU对肿瘤坏死因子-α(tumornecrosisfactor-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p(estrogenreceptorp,ER|3)抑制剂可阻断AU的抗凋亡作用,同时AU可使ERp表达升高.结论AU可以抑制由TNF-α诱导的CPC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.