树鼩脑缺血时神经元线粒体渗透性转导孔开放对线粒体呼吸的影响  

The opening of neuronal mitochondria permeability transition pore affects respiratory function during thrombotic cerebral ischemia in tree shrews

作　　者：张颖[1] 李树清[1] 刘跃[1] 

机构地区：[1]昆明医学院病理生理教研室,云南昆明650031

出　　处：《中国病理生理杂志》2004年第1期120-124,共5页Chinese Journal of Pathophysiology

基　　金：云南省自然科学基金资助 (No .2 0 0 1C0 0 64M)

摘　　要：目的 :揭示光化学诱导树鼠句脑缺血后不同时间内 ,缺血神经元线粒体呼吸功能的变化 ,观察血小板活化因子 (PAF)受体拮抗剂银杏内酯B(GB)和免疫抑制剂环孢菌素A (CsA)对线粒体呼吸及神经元线粒体渗透性转导孔 (MPT)开放的影响 ,探讨二者可能的神经保护机制及缺血时MPT开放与线粒体呼吸的相互关系。方法 :建立光化学诱导树鼠句脑缺血模型 ,分离缺血后 4、2 4、72h大脑皮层线粒体 ,用氧电极极谱法测定线粒体呼吸。于缺血 6h分别注射GB和CsA ,2 4h时观察相关指标。另取分离的线粒体 ,用CaCl2 诱导MPT开放 ,再分别加入CsA或GB ,观察其对线粒体肿胀的影响。结果 :缺血脑皮层神经元线粒体Ⅲ态呼吸速度、呼吸控制率 (RCR)及磷氧比 (P/O)逐渐下降 ,以缺血 2 4h的变化为著 ,与假手术组相比均有显著差异 (P <0 0 1)。给予GB或CsA ,Ⅲ态呼吸速度显著大于对照组(P <0 0 1) ,P/O比上升 (P <0 0 5)。CaCl2 可诱导MPT开放 ,线粒体肿胀而透光率迅速下降 ,CsA有效阻滞了MPT开放 ,GB则不然。结论 :光化学诱导树鼠句局灶脑缺血后 ,缺血皮层线粒体呼吸明显障碍 ,GB或CsA可不同程度地改善缺血神经元线粒体代谢 ,可能与GB拮抗神经细胞膜上PAF受体活化 ,间接调节线粒体呼吸有关 ;而CsA主要通过抑制MPT开放而改善线粒体呼吸而?AIM: The present study explored those changes in brain mitochondrial respiration in different times after thrombotic cerebral ischemia induced by photochemical reaction in primate's animal tree shrew and o bserved the effects of platelet-activating factor (PAF) receptor antagonist gin kgolide B (GB) and immunosuppressor cyclosporin A (CsA) on neuronal mitochondria l respiration and mitochondrial permeability transition pore(MPT) in twenty-four hours after occlusion and showed their neuronprotective mechanism and expatiate the relationship between mitochondrial respiration and MPT. METHODS: The focal thrombotic cerebral ischemia was formed by photochemistry-induce d technology in tree shrews. At 4,24,72 h after focal cerebral ischemia, the n euronal mitochondria were centrifuged. Clark oxygen electrode was used to measur e the changes in neuronal mitochondrial respiration.Pretreatment for experiment al animals with GB and CsA at 6h after occlusion, we centrifuged the mitochondri a and measured the changes in neuronal mitochondrial respiration at 24 h after o cclusion. In addition, experiments were performed in a flurometer by measuring CaCl 2 100 μmol/L induced centrifuged mitochondrial swelling and GB or CsA were added at the same time. RESULTS: All of respiration state Ⅲ, RCR and P/O decreased after cerebral ischemia. There were significant difference s between every ischemic group and sham, especially at 24 h (P<0 01). Pretr eatment for experimental animals with GB and CsA,the state Ⅲ and P/O recovere d after ischemia for 24 h (P<0 01,P<0 05). CaCl 2 induced the opening of MPT and the light scattering decreased. When CsA or GB were added at the initiation of each experiment, studies on the swelling kinetics of isolated brain mitochon dria showed the CsA but GB, inhibited calcium ions induced mitochondria swelling . CONCLUSIONS: Neuronal mitochondrial respiration and metabolism were inhibited after thrombotic cerebral ischemia induced by photochemical react ion. GB and CsA were shown to improve neu

关 键 词：脑缺血 神经元线粒体 呼吸功能 渗透性转导孔 银杏内酯B 树鼩科 环孢菌素 

分 类 号：R743.31[医药卫生—神经病学与精神病学]