依布硒啉对大鼠急性脊髓损伤后线粒体的保护作用

The Protective Effect of Ebselen on Mitochondrial Damage after Spinal Cord Injury in Rats

目的探讨依布硒啉对大鼠急性脊髓损伤后线粒体氧化损伤、细胞色素C释放及神经细胞凋亡的影响。方法将60只健康SD大鼠按随机数字表法分为5组,每组12只。采用Allen’s法制脊髓损伤(SCI)模型,假手术组仅行椎板切除,SCI模型组行椎板切除+打击,甲基泼尼松龙组打击后给予甲基泼尼松龙腹腔注射处理(30 mg/kg),依布硒啉组打击后给予依布硒啉腹腔注射处理(10 mg/kg),生理盐水组打击后给予等体积0.1%二甲基亚砜的生理盐水溶液腹腔注射处理。术后24 h取受损脊髓,检测丙二醛(MDA)、谷胱甘肽(GSH)含量、细胞色素C表达及神经细胞凋亡情况。结果依布硒啉组较SCI模型组脊髓组织线粒体中MDA含量明显降低,GSH明显升高,Western blot检测细胞色素C的释放量减少,TUNEL法检测神经细胞凋亡数目明显减少(均P<0.01)。结论依布硒啉能够改善SCI后线粒体氧化损伤,减少线粒体细胞色素C释放,抑制神经细胞凋亡,对SCI起到保护作用。

Objective To investigate the protective effect of Ebselen on mitochondrial damage and its influence to Cytochrome C expression and the neuronal apoptosis after spinal cord injury in rats. Methods Sixty adult SD rats were ran-domly divided into 5 groups （12 each group）. Spinal cord injury model was made using Allen＆#39;s method. Sham operation group received only laminectomy;SCI group received laminectomy and spinal trauma;Saline group received saline injection intraperitoneally （0.1%DMSO） after injury;methylprednisolone group received 30 mg/kg methylprednisolone injection intra-peritoneally, ebselen group received 10 mg/kg ebselen injection intraperitoneally. The malonaldehyde （MDA） and glutathi-one （GSH）level at the injured sites of the spinal cord were detected 24 hours after trauma, and the expression level of Cyto-chrome C was also observed. Finally, neuronal apoptosis was identified by TUNEL staining. Results MDA level in the Eb-selen group was significantly lower than that in the SCI group, and GSH level was significantly elevated in the Ebselen group compared with SCI group （P〈0.01）. Expression of Cytochrome C in Ebselen group was lower than that in SCI group shown by Western blot, and the neuronal apoptosis in Ebselen group reduced significantly too compared with SCI group （P〈0.01）. Conclusion Ebselen can alleviate peroxidation,prohibit expression of Cytochrome C and inhibit neuronal apoptosis,thus it shows a protective effect to experimental acute SCI.