地氟烷预先给药对大鼠前脑缺血再灌注时线粒体通透性转换孔和膜电位的影响  

Effects of desflurane pretreatment on mitochondrial permeability transition pore and membrane potential following forebrain ischemia-reperfusion in rats

作　　者：张兵[1] 魏霞[1] 李文志[1] 崔晓光[1] 丁文刚[1] 吴海玲[1] 

机构地区：[1]哈尔滨医科大学附属第二医院麻醉科哈尔滨医科大学麻醉基础理论与应用研究实验室,150086

出　　处：《中华麻醉学杂志》2008年第2期171-174,共4页Chinese Journal of Anesthesiology

摘　　要：目的研究地氟烷预先给药对大鼠前脑缺血再灌注时线粒体通透性转换孔（PTP）和膜电位的影响，以探讨其脑保护作用的机制。方法雄性Wistar大鼠40只，体重250～300g，随机分为4组（n=10）：假手术组（Ⅰ组）、缺血再灌注组（Ⅱ组）、1．0MAC地氟烷组（Ⅲ组）和1．5MAC地氟烷组（Ⅳ组），采用夹闭双侧颈总动脉合并低血压的方法建立前脑缺血再灌注损伤模型，Ⅲ组和Ⅳ组在缺血前分别吸入地氟烷1．0MAC和1．5MAC40min。再灌注4h行神经功能缺陷评分（NDS），迅速断头，密度梯度离心分离线粒体，采用分光光度计法分析Ca^2＋诱发的线粒体肿胀，荧光分光光度计法检测线粒体膜电位耗散。结果再灌注4h，与Ⅰ组相比，Ⅱ组、Ⅲ组和Ⅳ组线粒体PTP活性、NDS升高，Ⅱ组线粒体膜电位耗散增加（P〈0．05）；与Ⅱ组相比，Ⅲ组和Ⅳ组线粒体PTP活性、NDS及线粒体膜电位耗散降低（P〈0．05）。结论地氟烷预先给药可减轻大鼠前脑缺血再灌注损伤，改善再灌注时神经功能，可能与其抑制线粒体的肿胀、减少线粒体膜电位的耗散有关。Objective To investigate the effects of pretreatment with different concentrations of desflurane on the mitochondrial permeability transition pore （MDTP） and mitochondrial membrane potential （MMP） following forebrain ischemia-reperfusion （I/R） in rats and the possible mechanism. Methods Forty healthy male Wistar rats weighing 250-300 g were randomly divided into 4 groups （ n = 10 each） ： group Ⅰ sham operation; group Ⅱ I/R; group Ⅲ 1.0 MAC desflurane ＋ I/R and group Ⅳ 1.5 MAC desflurane ＋ I/R. Forebrain ischemia was induced by 10 rain occlusion of bilateral common carotid arteries combined with hypotension （MAP was maintained at 43-47 mm Hg）. In group Ⅲ and Ⅳ the animals inhaled 1.0 and 1 . 5 MAC desflurane for 40 rain respectively before forebrain I/R. The neurological deficit was scored （0 = normal, 100 = brain death） at 4 h reperfusion. The animals were then decapitated and their forebrains were immediately isolated and homogenized followed by density gradient centrifugation. The MPTP opening was assayed by spectrophotometry and MMP was assessed by fluoro- spectrophotometry. Results I/R significantly increased MPTP opening, MMP and neurological deficit score in groupⅡ , Ⅲ and Ⅳ as compared with sham operation group. Pretreatment with 1.0 or 1.5 MAC desflurane inhalation significantly attenuated 1/R-induced increase in MPTP opening, MMP and neurological deficit score in group Ⅲ and Ⅳ as compared with group Ⅱ but there was no significant difference between group Ⅲ and Ⅳ. Conclusion Pretreatment with 1.0 or 1.5 MAC desflurane inhalation an attenuate forebrain I/R induced injury and neurological deficit by inhibiting MDTP opening and decreasing MMP. The protective effect is independent of desflurane concentration.

关 键 词：脑缺血 再灌注损伤 线粒体 膜电位 地氟醚 

分 类 号：R96[医药卫生—药理学]