打开APP

Eur.Heart.J:何奔等发现心肌缺血再灌注损伤新机制

  1. 心肌缺血再灌注

来源:医学论坛网 2012-11-18 10:52

近日,《欧洲心脏期刊》(European Heart Journal)在线发表了上海交通大学医学院附属仁济医院心内科何奔教授领衔的课题组的最新研究成果,他们发现心肌缺血再灌注损伤新机制。 心肌缺血再灌注损伤是临床心脏病学的重要问题,缺血的心肌在血管开放后导致了比血管闭塞时更严重的急性损伤,临床上会导致严重的心律失常,心肌坏死面积扩大,心脏破裂甚至死亡。

近日,《欧洲心脏期刊》(European Heart Journal)在线发表了上海交通大学医学院附属仁济医院心内科何奔教授领衔的课题组的最新研究成果,他们发现心肌缺血再灌注损伤新机制。

心肌缺血再灌注损伤是临床心脏病学的重要问题,缺血的心肌在血管开放后导致了比血管闭塞时更严重的急性损伤,临床上会导致严重的心律失常,心肌坏死面积扩大,心脏破裂甚至死亡。因此,探讨引起再灌注损伤的机制,寻找有效的药物减轻这一损伤过程,对临床急性心肌梗死的救治有十分重要的意义。
 
何奔教授,卜军博士首先在新生大鼠的心肌细胞中发现一种叫FXR的原本存在于胃肠道与胆道系统的细胞核受体;进而研究者对这一核受体在心肌细胞中的功能进行了深入的探讨,发现FXR受体虽然在新生大鼠的心肌有表达,但成年后这一表达明显降低,而当心肌遭受缺血并进行再灌注时,FXR的表达出现明显的增加。研究者进一步通过各种科学的方法,证明该核受体通过与心肌细胞中主管细胞呼吸功能的线粒体相互作用,导致线粒体功能失常而促进细胞凋亡;而此时抑制或取消FXR的功能,可以明显减轻心肌缺血再灌注损伤,降低心肌梗死面积。
 
据卜军博士介绍,“心肌缺血再灌注损伤是临床心脏病领域经久不衰的重要热点,细胞核受体与细胞内第二信息传导系统是全世界临床药物开发的两个最大靶向系统,该项研究的发现对临床深入理解缺血再灌注损伤的机制,开发防治缺血再灌注损伤的药物具有重要的意义”。(生物谷Bioon.com)

Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury
 
Jun Pu1, Ancai Yuan, Peiren Shan, Erhe Gao, Xiaoliang Wang, Yajing Wang, Wayne Bond Lau, Walter Koch, Xin-Liang Ma, and Ben He

Aims Emerging evidence indicates that nuclear receptors play a critical regulatory role in cardiovascular physiology/pathology. Recently, farnesoid-X-receptor (FXR), a member of the metabolic nuclear receptor superfamily, has been demonstrated to be expressed in vascular cells, with important roles in vascular physiology/pathology. However, the potential cardiac function of FXR remains unclear. We investigated the cardiac expression and biological function of FXR. Methods and results Farnesoid-X-receptor was detected in both isolated neonatal rat cardiac myocytes and fibroblasts. Natural and synthetic FXR agonists upregulated cardiac FXR expression, stimulated myocyte apoptosis, and reduced myocyte viability dose- and time-dependently. Mechanistic studies demonstrated that FXR agonists disrupted mitochondria, characterized by mitochondrial permeability transition pores activation, mitochondrial potential dissipation, cytochrome c release, and both caspase-9 and -3 activation. Such mitochondrial apoptotic responses were abolished by siRNA-mediated silencing of endogenous FXR or pharmacological inhibition of mitochondrial death signalling. Furthermore, low levels of FXR were detected in the adult mouse heart, with significant (~2.0-fold) upregulation after myocardial ischaemia/reperfusion (MI/R). Pharmacological inhibition or genetic ablation of FXR significantly reduced myocardial apoptosis by 29.0–53.4%, decreased infarct size by 23.4–49.7%, and improved cardiac function in ischaemic/reperfused myocardium. Conclusion These results demonstrate that nuclear receptor FXR acts as a novel functional receptor in cardiac tissue, regulates apoptosis in cardiomyocytes, and contributes to MI/R injury.

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->