促红细胞生成素在脑缺血再灌注损伤中对线粒体的保护作用  

Protective effect of erythropoietin on neuronal mitochondrial function against cerebral ischemia/ reperfusion injury in rats

作　　者：杨彬源[1] 全伟[1] 曹志恺[1] 丁正斌[1] 张昊[1] 陈凡帆[1] 吕建平[1] 

机构地区：[1]广州医学院附属广州市第一人民医院神经外科,广州510180

出　　处：《中华神经医学杂志》2008年第9期894-898,共5页Chinese Journal of Neuromedicine

摘　　要：目的探讨促红细胞生成素（EPO）在脑缺血再灌注损伤中对线粒体功能的保护作用。方法30只SD大鼠按随机数字表法分为正常对照组、缺血再灌注组和EPO治疗组3组，每组各10只。EPO治疗组和缺血再灌注组用线栓法复制脑缺血再灌注模型。EPO治疗组在缺血再灌注后1、24、48、60h腹腔注射EPO，剂量为3000U／kg（用生理盐水以1：1比例稀释），缺血再灌注组腹腔注射同等剂量的生理盐水。正常对照组仅分离颈部动脉，动脉不做栓塞处理。缺血后72h观察各组大鼠脑组织神经细胞线粒体跨膜电位、线粒体丙二醛、超氧化物歧化酶、Na^＋-K^＋-ATP酶活性、一氧化氮含量和免疫组化检测海马区Caspase-3阳性细胞数的变化。结果EPO治疗组的神经细胞线粒体跨膜电位（77.48±5．93）、超氧化物歧化酶[（96．91±8．66）μkat／g]、Na^＋-K^＋-ATP酶活性[（10．48±2．77）μkat／g]明显高于缺血再灌注组[44．47±17．35、（84．46±8．54）μkat／g、（7．37±2．87）μkat／g]，线粒体丙二醛[（37．99±5．38）μmolg]、一氧化氮含量[（10．18±2．02）μmol/g]、Caspase-3阳性细胞数（66．31±8．09）明显低于缺血再灌注组[（44．83±6．48）μmol/g、（12．12±2．14）μmol／g、74．90±7．42]。结论EPO对缺血再灌注损伤脑组织产生保护作用的重要机制之一是保护神经细胞线粒体的功能，其核心是抑制线粒体跨膜电位的下降。Objective To investigate the protective effect of erythropoietin （EPO） on the mitochondria in the brain neurons against cerebral ischemia/reperfusion （IR） injury in rats. Methods Thirty SD rats are randomly allocated into 3 groups, namely the EPO group （n=10）, IR group （n=10）, and sham operation group （n=10）. In EPO group and IR group, the rats were subjected to middle cerebral artery occlusion （MCAO） to induce cerebral IR injury, followed by treatment with intraperitonal EPO injection at 3000 U/kg and the same volume of saline, respectively. In the sham operation group, the carotid artery was only isolated without MCAO or subsequent treatment. Seventy-two hours after the IR injury, the mitochondrial membrane potential in the neurons was detected, and the changes in superoxide dismutase （SOD） activity, malondialdehyde （MDA） and nitric oxide （NO） concentrations, and Na^＋-K^＋-ATPase activity in the neuronal mitochondria were determined. The number of caspase-3-positive neurons in the hippocampus was observed immunohistochemically. Results The mitochondrial membrane potential and activities of SOD and Na^＋-K^＋-ATPase were significantly higher, whereas the MDA and NO concentrations and the number of caspase-3-postive neurons significantly lower in EPO group than in IR group after the treatment. Conclusion Protecting the neuronal mitochondrial fimction is one of the important mechanisms of EPO for brain protection against IR injury, and this mitochondrial protection effect is mediated essentially by stabilizing the mitochondrial membrane potential.

关 键 词：促红细胞生成素 缺血再灌注损伤 线粒体 

分 类 号：R741[医药卫生—神经病学与精神病学]