天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (12): 1373-1376.doi: 10.11958/j.issn.0253-9896.2015.12.008

• 实验研究 • 上一篇    下一篇

Exendin-4 对大鼠脊髓损伤后氧化应激和神经细胞凋亡的影响

赵兴长，李昊天，王继权，孙平，褚鑫，吕刚，范仲凯△   

  1. 辽宁医学院附属第一医院骨科(邮编121001)
  • 收稿日期:2015-06-23 修回日期:2015-07-30 出版日期:2015-12-15 发布日期:2015-12-11
  • 通讯作者: △通讯作者E-mail:flanzz@163.com E-mail:xingzhang169@163.com
  • 作者简介:赵兴长（1989），男，硕士在读，主要从事脊髓损伤的机制及修复研究
  • 基金资助:
    国家自然科学基金资助项目(81272074)；辽宁省高等学校优秀人才支持计划项目(LJQ2014091)；辽宁医学院校长基金 (AH2014012)

Effect of Exendin-4 on oxidative stress and neural apoptosis following spinal cord injury

ZHAO Xingzhang, LI Haotian, WANG Jiquan, SUN Ping, CHU Xin, LYU Gang, FAN Zhongkai△   

  1. Department of Orthopedics, First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, China
  • Received:2015-06-23 Revised:2015-07-30 Published:2015-12-15 Online:2015-12-11
  • Contact: △Corresponding Author E-mail：flanzz@163.com E-mail:xingzhang169@163.com

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摘要： 目的研究Exendin-4 对大鼠脊髓损伤后氧化应激和神经细胞凋亡的作用。方法成年雄性SD 大鼠36 只（体质量200~250 g）随机分为3 组（n=12）：假手术组（Sham 组）、单纯脊髓损伤组（SCI 组）、Exendin-4 组（Ex-4 组）。Sham 组只暴露脊髓，不打击；SCI 组和Ex-4 组均采用Allen′s 重物打击法制作脊髓损伤模型；Ex-4 组在脊髓损伤后立即腹腔内注射Exendin-4 溶液，剂量10 μg/只；SCI 组和Sham 组均注射等体积生理盐水。在24 h 后检测各组脊髓组织中丙二醛（MDA）含量和过氧化氢酶（CAT）活性，TUNEL 法检测神经细胞凋亡情况，Western blot 检测 caspase-9 和凋亡诱导因子（AIF）的表达情况。结果与Sham 组相比，SCI 组脊髓组织中的MDA 含量明显增加， caspase-9 和AIF 表达水平明显增加，神经细胞凋亡比例明显升高，CAT 活性明显降低（P < 0.01）。与SCI 组相比， Ex-4 组脊髓组织中MDA 含量明显降低，caspase-9 和AIF 表达水平明显降低，神经细胞凋亡比例明显降低，CAT 活性明显升高（P < 0.01）。结论大鼠脊髓损伤后，Exendin-4 可通过减轻氧化损伤抑制神经细胞凋亡。

关键词: 脊髓损伤, 氧化性应激, 细胞凋亡, 胰高血糖素样肽1, 大鼠, Sprague-Dawley, Exendin-4

Abstract: Abstract: Objective To study the effect of Exendin-4 on oxidative stress and neural apoptosis following spinal cord injury (SCI). Methods Adult male SD rats, with weight between 200-250 g, were randomly divided into three groups (12 in each group): Sham group, SCI group and Exendin-4 group (Ex-4 group). Rats in Sham group achieved spinal cord exposure. SCI group and Ex-4 group were induced according to Allen′s test (using a weight-drop device). Rats in Ex-4 group were ad⁃ ministrated with Exendin-4 (10 μg/rat) through intraperitoneal injection immediately after establishment of SCI models. Rats in Sham group and SCI group were given the same volume of normal saline solution instead. Level of malondialdehyde (MDA) and the activity of catalase (CAT) were assessed in spinal cord tissues 24 hour after drug administrations. Neural apoptosis was detected by TUNEL staining and the expression levels of caspase-9 and AIF were determined using Western blot. Results Compared with Sham group, the levels of MDA, caspase-9 and AIF as well as neuronal apoptosis rate in⁃ creased obviously, while activity of CAT decreased markedly in SCI group（P < 0.01）. Compared with SCI group, the levels of MDA, caspase-9 and AIF as well as the neuronal apoptosis rate decreased obviously, while activity of CAT increased re⁃ markably in Exendin-4 group（P < 0.01）. Conclusion Exendin-4 restrain neural apoptosis following spinal cord injury through relieving oxidative damage.

Key words: spinal cord injuries, oxidative stress, apoptosis, glucagon-like peptide 1, rats, Sprague-Dawley, Exendin-4