CAJ | 학술논문

目的：检测选择性线粒体分裂抑制剂-1（Mdivi-1）对大鼠急性脊髓损伤（ASCI）后神经细胞线粒体中丙二醛（MDA）、谷胱甘肽（GSH）、细胞色素C（Cyt-C）及神经细胞凋亡的影响。方法成年雌性SD大鼠36只，体质量250~300 g，随机分为假手术组（Sham组）、单纯脊髓损伤组（SCI组）、Mdivi-1预处理组（1.20 mg/kg，Mdivi-1组），各12只。Sham组只暴露脊髓，不打击。SCI组和Mdivi-1组采用Allen’s方法制备脊髓损伤模型。Mdivi-1组在脊髓打击之前15 min尾静脉给予Mdivi-1，而SCI组给予等量二甲基亚砜（DMSO）。Sham组在暴露脊髓8 h后立即处死，SCI组和Mdivi-1组均于脊髓损伤后8 h处死；然后取出脊髓节段T9~T11，用分光光度计检测各组脊髓组织线粒体中MDA和GSH的含量，Western Blot法检测线粒体及胞浆内Cyt-C表达情况，荧光TUNEL法观察神经细胞凋亡情况。结果与Sham组相比，SCI组线粒体中Cyt-C和GSH明显减少，但线粒体中的MDA，胞浆中Cyt-C及神经细胞凋亡数目明显增多（P<0.01）；与SCI组相比，Mdivi-1组线粒体中Cyt-C和GSH明显增多，但线粒体中MDA，胞浆中Cyt-C以及神经细胞凋亡数目明显减少（P<0.01）。结论 Mdivi-1具有减轻ASCI后神经细胞线粒体氧化损伤，抑制线粒体中Cyt-C的释放及神经细胞凋亡的作用，促进了脊髓功能恢复。
목적：검측선택성선립체분렬억제제-1（Mdivi-1）대대서급성척수손상（ASCI）후신경세포선립체중병이철（MDA）、곡광감태（GSH）、세포색소C（Cyt-C）급신경세포조망적영향。방법성년자성SD대서36지，체질량250~300 g，수궤분위가수술조（Sham조）、단순척수손상조（SCI조）、Mdivi-1예처리조（1.20 mg/kg，Mdivi-1조），각12지。Sham조지폭로척수，불타격。SCI조화Mdivi-1조채용Allen’s방법제비척수손상모형。Mdivi-1조재척수타격지전15 min미정맥급여Mdivi-1，이SCI조급여등량이갑기아풍（DMSO）。Sham조재폭로척수8 h후립즉처사，SCI조화Mdivi-1조균우척수손상후8 h처사；연후취출척수절단T9~T11，용분광광도계검측각조척수조직선립체중MDA화GSH적함량，Western Blot법검측선립체급포장내Cyt-C표체정황，형광TUNEL법관찰신경세포조망정황。결과여Sham조상비，SCI조선립체중Cyt-C화GSH명현감소，단선립체중적MDA，포장중Cyt-C급신경세포조망수목명현증다（P<0.01）；여SCI조상비，Mdivi-1조선립체중Cyt-C화GSH명현증다，단선립체중MDA，포장중Cyt-C이급신경세포조망수목명현감소（P<0.01）。결론 Mdivi-1구유감경ASCI후신경세포선립체양화손상，억제선립체중Cyt-C적석방급신경세포조망적작용，촉진료척수공능회복。
Objective To detect the effects of the selective mitochondrial fission inhibitor-Mdivi-1 on the malondi-alolehyde (MDA), glutathione (GSH) as well as cytochrome C (Cyt-C) in neuronal mitochondria and neuronal apoptosis. Methods Thirty-six adult female SD rats (250-300 g) were randomly divided into 3 groups (n=12):sham operation (Sham) group, single spinal cord injury (SCI) group and Mdivi-1 pretreatment (1.20 mg/kg, Mdivi-1) group. In sham group, the rats’ spinal cord was exposed, but no hit. The rat model of spinal cord injury was established by Allen’s method in SCI group and Mdivi-1 group. In Mdivi-1 group, rats were given Mdivi-1 through the tail vein 15 min before spinal cord injury, and SCI group received the same amount of dimethyl sulfoxide (DMSO). Rats in Sham group were sacrificed 8 h after exposing spinal cord. Rats in SCI group and Mdivi-1 group were sacrificed at 8 h after the spinal cord injury, then were removed the spinal cord T9-11. The contents of MDA and GSH in mitochondria of spinal cord tissues were detected with spectrophotometer. The expressions of Cyt-C protein in the mitochondria and cytoplasm were detected by Western blot assay. The neuronal apoptosis was assessed by TUNEL staining. Results Compared with Sham group, levels of Cyt-C and GSH in mitochondria were decreased significantly (P<0.01), while levels of MDA in mitochondria, Cyt-C in cytoplasm and the neuronal apopto-sis were increased significantly in SCI group (P<0.01). Compared with SCI group, Cyt-C and GSH levels in mitochondria were increased significantly in Mdivi-1 group (P<0.01), however, MDA in mitochondria,Cyt-C in cytoplasm and the neuro-nal apoptosis were significantly reduced (P<0.01). Conclusion Mdivi-1 can relieve neurons from mitochondrial oxidative damage, inhibit the release of cytochrome C and neuronal apoptosis after acute spinal cord injury, which plays a role in pro-moting the recovery of spinal cord function.