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Mechanism for Protective Effects of Selective Mitochondrial Fission Inhibitor on Neurons after Acute Spinal Cord Injury in Rats

  

  • Received:2014-03-25 Revised:2014-04-03 Published:2014-07-15 Online:2014-07-15

Abstract:

[Abstract] Objective To detect the effects of the selective mitochondrial fission inhibitor-Mdivi-1on 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 (250-300g) were randomly divided into3groups (n=12): sham operation (Sham) group, single spinal cord injury (SCI) group and Mdivi-1pretreatment (1.20mg/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-1group. In Mdivi-1group, rats were given Mdivi-1through the tail vein 15min before spinal cord injury, and SCI group received the same amount of dimethyl sulfoxide (DMSO). Rats in Sham group were sacrificed8h after exposing spinal cord. Rats in SCI group and Mdivi-1group were sacrificed at8h 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-1group (P<0.01), however, MDA in mitochondria,Cyt-C in cytoplasm and the neuro? nal apoptosis were significantly reduced (P<0.01). Conclusion Mdivi-1can 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.

Key words: acute spinal cord injury, mdivi-1, malondialolehyde, glutathione, cytochrome C, apoptosis