Abstract: Objective To compare the effects of different doses of FTY720 on inhibiting expression of Caspase-3 and neural apoptosisin rats with acute spinal cord injury (SCI), and find out the suitable dose. Methods 200 female SD rats were randomly divided into 5 groupswith 40 in each group. Group A (laminectomy but not contusion) were administered 0.3 ml normal saline by gavage. SCI model was establishedby Allen's WD method at the T9 level of spinal cord in other groups. Group B were administered 0.3 ml normal saline after modeling.Groups C, D and E were administered 0.3 ml FTY720- saline solution of 1, 3 and 5 mg/kg respectively. All the groups were sacrificed at 6 h,12 h, 24 h, 48 h, 72 h (n=8, per each time-point). Caspase-3 expression was detected with streptavidin-peroxidase immunohistochemistry,and neural apoptosis was detected with the TUNEL method. Results Positive Caspase-3 expression and neural apoptosis were not observedin Group A at 6 h. In Groups B、C、D and E, the number of apoptotic cells increased with increased time of acute SCI, peaked at 24 h afterinjury, and then gradually reduced. Caspase-3 expression was at equal pace with neural apoptosis. The difference of the number of apoptoticand Caspase-3 expression cells among all groups were significant, with the order Group B>Group C>Group D>Group A (P<0.05). However,there was no significant difference between Group D and Group E (P>0.05). The number of apoptotic and Caspase-3 expression cells negativelycorrelated with the dose of FTY720 when the dose was less than 3 mg/kg (P<0.05), and there was no relationship when the dose wasmore than 3 mg/kg (P>0.05). Conclusion FTY720 significantly reduces Caspase-3 expression and neural apoptosis in rats with acute SCI.There is a dose-effect relationship between the dose of FTY720 and the Caspase-3 expression and neural apoptosis. It's indicated that 3 mg/kg is the most appropriate dosage.

Key words: FTY720, Caspase-3, apoptosis, spinal cord injury, neural regeneration, dose, dose-effect relationship