坏死抑制素的心脏保护作用需要线粒体通透性转换孔的亲环素-D成分。
The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore.
作者信息
Lim S Y, Davidson S M, Mocanu M M, Yellon D M, Smith C C T
机构信息
The Hatter Cardiovascular Institute, University College London Hospital and Medical School, 67 Chenies Mews, London, WC1E 6HX, UK.
出版信息
Cardiovasc Drugs Ther. 2007 Dec;21(6):467-9. doi: 10.1007/s10557-007-6067-6.
BACKGROUND
Necrostatin (Nec-1) protects against ischemia-reperfusion (IR) injury in both brain and heart. We have previously reported in this journal that necrostatin can delay opening of the mitochondrial permeability transition pore (MPTP) in isolated cardiomyocytes.
AIM
The aim of the present study was to investigate in more detail the role played by the MPTP in necrostatin-mediated cardioprotection employing mice lacking a key component of the MPTP, namely cyclophilin-D.
METHOD
Anaesthetized wild type (WT) and cyclophilin-D knockout (Cyp-D-/-) mice underwent an open-chest procedure involving 30 min of myocardial ischemia and 2 h of reperfusion, with subsequent infarct size assessed by triphenyltetrazolium staining. Nec-1, given at reperfusion, significantly limited infarct size in WT mice (17.7 +/- 3% vs. 54.3 +/- 3%, P < 0.05) but not in Cyp-D-/- mice (28.3 +/- 7% vs. 30.8 +/- 6%, P > 0.05).
CONCLUSION
The data obtained in Cyp-D-/- mice provide further evidence that Nec-1 protects against myocardial IR injury by modulating MPTP opening at reperfusion.
背景
坏死抑制剂（Nec-1）可保护脑和心脏免受缺血再灌注（IR）损伤。我们之前曾在本期刊报道，坏死抑制剂可延迟离体心肌细胞中线粒体通透性转换孔（MPTP）的开放。
目的
本研究旨在更详细地研究MPTP在坏死抑制剂介导的心脏保护作用中所起的作用，采用缺乏MPTP关键成分亲环蛋白D的小鼠进行研究。
方法
对麻醉的野生型（WT）和亲环蛋白D基因敲除（Cyp-D-/-）小鼠进行开胸手术，包括30分钟心肌缺血和2小时再灌注，随后通过三苯基四氮唑染色评估梗死面积。在再灌注时给予Nec-1，可显著限制WT小鼠的梗死面积（17.7±3%对54.3±3%，P<0.05），但对Cyp-D-/-小鼠则无此作用（28.3±7%对30.8±6%，P>0.05）。
结论
在Cyp-D-/-小鼠中获得的数据进一步证明，Nec-1通过调节再灌注时MPTP的开放来保护心肌免受IR损伤。
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