选择性线粒体分裂抑制剂抑制大鼠急性脊髓损伤后的细胞凋亡  

Inhibition of apoptosis through selective mitochondrial fission inhibitor after acute spinal cord injury in rats

作　　者：李刚[1] 范仲凯[1] 贾志强[1] 赵兴长 李昊天[1] 邢恩福[1] 吕刚[1] 

机构地区：[1]辽宁医学院附属第一医院骨科,辽宁锦州121001

出　　处：《基础医学与临床》2014年第11期1486-1490,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81272074);辽宁省博士科研启动基金(20121094);辽宁医学院校长基金(XZJJ20130204)

摘　　要：目的检测mdivi-1预处理对大鼠急性脊髓损伤(ASCI)后线粒体膜电位,凋亡诱导因子(AIF)释放及细胞凋亡的影响。方法大鼠随机分为:假手术组(Sham组)、单纯脊髓损伤组(SCI组)、二甲基亚砜预处理组(DMSO组),mdivi-1预处理组(mdivi-1组)。采用Allen's方法制备ASCI模型。JC-1标记法检测线粒体膜电位(MMP),Western blot方法检测线粒体及细胞核内AIF,TUNEL法检测细胞凋亡。结果与Sham组相比,SCI组线粒体中AIF先降低后升高,最低点是8h(P<0.01),而细胞核中AIF却呈相反趋势(P<0.01),术后8 h MMP明显降低(P<0.01),凋亡细胞数目明显增多(P<0.01)。与SCI 8 h组相比,mdivi-1组MMP明显升高(P<0.01),线粒体中AIF明显增多(P<0.01),细胞核中AIF明显降低(P<0.01),凋亡细胞数目明显减少(P<0.01)。结论 Mdivi-1具有保护大鼠ASCI后MMP,抑制线粒体中AIF的释放和细胞凋亡的作用。Objective To detect the effects of the pretreatment of mdivi-1on mitochondrial membrane potential,the release of AIF and apoptosis after acute spinal cord injury （ASCI） in rats.Methods Rats were randomly divided into sham operation group （Sham group）,single spinal cord injury group （SCI group）,DMSO pretreatment group （DMSO group）,mdivi-1 pretreatment group （mdivi-1 group）.Allen＇s weight drop method was used to establish ASCI rat model at T10 section.The content of AIF protein in the mitochondria and nucleus in spinal cord of rats was detected by Western blot.Mitochondrial membrane potential was deteced by JC-1 labeling.The number of apoptotic cells was assessed by TUNEL staining.Results Compared with Sham group,AIF in mitochondria of SCI group reduced first,then increased,and the lowest point was 8 h（P ＜0.01） ; while AIF in the nucleus showed the opposite trend（P ＜0.01） ; The mitochondrial membrane potential significantly decreased,while the number of apoptotic cells increased significantly at 8 h after ASCI（P ＜0.01）.Compared with SCI group,in mdivi-1 group,the mitochondrial membrane potential,AIF in mitochondria increased significantly （P ＜0.01）,however,AIF in nucleus （P ＜0.01） and the number of apoptotic cells reduced significantly at 8 h after ASCI （P ＜0.01）.Conclusions Mdivi-1 can protect mitochondrial membrane potential,inhibit the release of AIF in mitochondria and the apoptosis after acute spinal cord injury.

关 键 词：急性脊髓损伤 线粒体膜电位 凋亡诱导因子 细胞凋亡 mdivi-1 

分 类 号：R651.2[医药卫生—外科学]