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

ABSTRACT

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.