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

基础医学与临床 ›› 2014, Vol. 34 ›› Issue (11): 1486-1490.

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

李刚,范仲凯,贾志强,赵兴长,李昊天,邢恩福,吕刚

辽宁医学院第一附属医院骨外科

收稿日期:2014-06-30 修回日期:2014-09-17 出版日期:2014-11-05 发布日期:2014-11-03
通讯作者: 吕刚 E-mail:ganglv_jz@163.com
基金资助:
脊髓损伤后针对神经细胞线粒体的靶向治疗研究;脊髓损伤后神经细胞线粒体形态动态改变特点及干预研究;神经细胞线粒体动态改变在脊髓损伤中的作用及机制

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

Received:2014-06-30 Revised:2014-09-17 Online:2014-11-05 Published:2014-11-03

摘要/Abstract

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-I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8h MMP明显降低（P<0.01），凋亡细胞数目明显增多（P<0.01）。与SCI 8h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。

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

Abstract: 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 were assessed by TUNEL staining. Results Compared with Sham group , AIF in mitochondria of SCI group reduced first, then increased ,and the lowest point is 8h(P<0.01); while AIF in the nucleus showed the opposite trend(P<0.01); The mitochondrial membrane potential decreased significantly, while the number of apoptotic cells increased significantly at 8h 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 8h after ASCI (P<0.01). Conclusion Mdivi-1 can protect mitochondrial membrane potential, inhibit the release of AIF in mitochondria and the apoptosis after acute spinal cord injury.

Key words: acute spinal cord injury, mitochondrial membrane potential, apoptosis-inducing factor, apoptosis, Mdivi-1

中图分类号:

R651.2

李刚范仲凯贾志强赵兴长李昊天邢恩福吕刚. 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[J]. 基础医学与临床, 2014, 34(11): 1486-1490.

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