| Objective: To observe the effects of a new immunosuppressant FTY720on lipidperoxidation after acute spinal cord injury(ASCI) in rats, and to investigate itsneuroprotective mechanism for ASCI from the aspect of free radicals-induced lipidperoxidation.Methods: A total of105female SD rats were equally divided into3groups,35foreach group. A group,only received opening vertebral plate, neither injured nor treated. Band C groups were subjected to a weight-drop contusion at T10(2g×12.5cm). At5min,3d and6d after injury, the rats in the B group were received IP injection of FTY720solution (1mg/kg), while the rats in the C group were received the same volume ofnormal saline at the same timepoints.The recovery of neurological function of the new immunosupressant FTY720afterACSI were observed using the BBB Scores and the Inclined Plane Test. The degree ofthe lipid peroxidation in blood were observed through the detection of serum SODactivity and MDA levels. The serum SOD activity and MDA levels were detected viaxanthine oxidase method and thiobarbituric method respectively. The histologicalchanges of the spial cord tissue were observed under light microscopy via HE staining.All the data were analyzed by using the Statistical Package for the Social Sciences18.0.The difference between the three groups were analyzed using the one-way analysis ofvariance(ANOVA). Measurement data were expressed as the mean values±standarddeviation. A value of P <0.05was considered statistically significant.Results: Before operation, all animals received mean (BBB scores) of21,indicating normally ambulating rats. During the acute and intermediate recovery stages,the FTY720-treated group showed significantly improved hind limb performance as compared to the saline-treated control group(P<0.01). This superior recovery continuedthroughout all of the time points. Although BBB scores in the sham group weresignificantly higher than the control and the FTY720-treated groups at days1,3and7post-operation(P<0.01), there was no statistical difference in mean BBB scores betweenthe FTY720-treated and the sham groups at days14post-operation. Preoperatively, allanimals showed mean the maximum angle of the inclined plate test approximately65degrees. Postoperatively, the mean of the maximum angle obviously decreased in thecontrol and FTY720-treated groups, and then gradually increased for the two groups,but consistently lower than the sham group (P<0.01). The FTY720-treated groupshowed significantly increased the maximum angle of the inclined plate test comparedto the control group at any time point post-operation (P<0.01). There was no statisticaldifference in the maximum angle of the inclined plate between the FTY720-treated andthe sham groups at days14post-operation.Superoxide dismutase activity was significant lower in the two SCI model groupsat3hours post-surgery compared to pre-operative measures. Serum SOD activitycontinued to decrease, reaching a minimum value at3days post-operation beforestarting to rise. The FTY720-treated group exhibited significantly higher SOD activitythan the saline-treated group at all time points (P<0.05at3,6, and24h post-surgery;P<0.01at12h and days3,7, and14). Furthermore, there was no statistical difference inSOD activity between the FTY720-treated group and sham group on day14day. TheFTY720-treated and saline-treated rats exhibited a sharp increase in MDA levels3hours post-surgery; however, serum MDA was significantly lower in theFTY720-treated group at all time points following injury (P<0.05at3,6, and24h;P<0.01at12h and days3,7, and14). Again, there was no statistical difference in MDAlevels between the FTY720-treated group and the sham group by day14.Spinal cord structures of the sham groups were clear,and no bleeding,dgeneration,edema, necrosis and other manifestations.At24h post-injury, FTY720and injury groupswere clearly visible hemorrhage and edema. At3d post-injury, neuronal swelling,rupture and dissolve. At7d post-injury, the edema and liquefied spinal cord region inthe injury group were further deteriortion. Gray matter was damaged seriously. At14dpost-injury, parts of the neurons have shown died and nuclear pyknosis in the injurygroup. The injuried center formed a necrotic cavity,and the edge region could seen theproliferation of glial cells. The white matter was only part of the normal structure, andshowing a large number of inflammatory cells.The range of the edema and liquefied necrsis in FTY720-treated group was obviously smaller compared to the injury group.The extent of damage of the gray and white matter was also lighter than the injury group,moreover, fewer inflammatory cells than the laterConclusion: The motor neural functional recovery after ASCI in rats can beeffectively promoted with the treatment of the new immunosuppressant FTY720. Thesecondary spinal cord injury caused by free ridicals-induced lipid peroxidation can beeffectively reduced with the treatment of the new immunosuppressant FTY720. |
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