摘要
目的:研究正常和缺血脑线粒体对环孢菌素A(CsA)的反应,并观察线粒体ATP敏感性钾通道与线粒体渗透性转换孔的关系。方法:本实验采用分光光度法,在分离线粒体上观察线粒体渗透性转换孔抑制剂和线粒体ATP敏感性钾通道开放剂对正常与缺血脑线粒体肿胀的影响。结果:在正常脑线粒体,0.5μmol/L和1μmol/LCsA以及30μmol/L二氮嗪(DE)均可明显减轻Ca2+诱导的线粒体肿胀程度,苍术苷(Atr)能取消此作用,而5μmol/LCsA不能减轻线粒体的肿胀。在全脑缺血5min后的线粒体,0.5μmol/LCsA可减轻Ca2+诱导的线粒体肿胀,该作用可被Atr取消,但1μmol/LCsA不能减轻肿胀;30μmol/LDE也可明显减轻Ca2+诱导的缺血脑线粒体肿胀程度,100μmol/L和200μmol/L5-羟基癸酸盐(5-HD)和Atr均可取消其作用。结论:缺血脑线粒体对线粒体渗透性转换孔开放的抑制剂比正常脑线粒体更为敏感,脑线粒体ATP敏感性钾通道激活可能是抑制线粒体渗透性转换孔开放的调控机制之一。
AIM： The purpose of this study was to investigate the effect of cyclosporin A on the isolated mitochondria from normal and ischemic rat brains and to observe the possible effect of mitochondrial ATP sensitive potassium channel on mitochondrial permeability transition. METHODS： The swelling of mitochondria isolated from normal and ischemic rat brain was evaluated by spectrophotometry. RESULTS： Cyclosporin A at concentrations of 0. 5 μmol/L or 1μmol/L and diazoxide at concentration of 30μmol/L significantly decreased the swelling of the normal brain mitochondria induced by 200μmol/L calcium, which was abolished by atractyloside at 100μmol/L. However, cyclosporin A at concentration of 5μmol/L did not affect the mitochondrial swelling. On the mitochondria isolated from ischemic brain, cyclosporin A at 0.5μmol/L but not 1μmol/L significantly decreased the mitochondrial swelling, which was cancelled by atractyloside at concentration of 100μmol/L. Diazoxide at concentration of 30 mol/L had the similar effect with cyclosporin A at 0. 5μmol/L, which was blocked by atractyloside at 100μmol/L or 5 - hydroxydecanoate at 100μmol/L and 200μmol/L CONCLUSIONS： Compared with the mitochondria isolated from normal brain, mitocliondria from ischemic brain are more sensitive to the inhibition of mitochondria permeability transition pore opening. Activation of mitochondrial ATP potassium channel may be one of the mechanisms by which the opening of mitochondrial permeability transition pine is inhibited.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2007年第1期155-159,共5页
Chinese Journal of Pathophysiology
基金
浙江省教育厅科研项目(No.20030306)
浙江大学医学院中青年科研启动基金资助项目
关键词
线粒体渗透性转换孔
钾通道
ATP敏感
脑缺血
环孢菌素
Mitochondrial permeability transition pore
Potassium channels, ATP sensitive
Brain ischemia
Cyclosporine
作者简介
Tel：0571-87217146；E-mail：xiaqing@xju.edu.cn
