Abstract：Objective To investigate the effect and mechanism of FTY720 in protecting the motor nerve function in rats with acute spinal cord injury (ASCI).Methods A model of ASCI in the rat was established using Allen' s method.The rats were divided into five groups according to random number table:Group A (normal control group,n =6),Group B (sham group,n =27),Group C (ASCI group,n =27),Group D (FTY720 systemic treatment group,n =27) and Group E (FTY720 topical treatment group,n =27).After treatment,each group was observed for the changes of lymphocytes in peripheral blood and topical spinal cord tissue,BBB score,pathological changes of spinal cord tissue and expression intensity of glial fibrillary acidic protein (GFAP).Results After ASCI in rats,the infiltration of local T lymphocyte subpopulations CD3,CD4 and CD8 was promoted,but the number of peripheral blood T lymphocyte subpopulations CD3,CD4 and CD8 was decreased.After FTY720 therapy,both local and peripheral blood lymphocytes were reduced in number and the decrease of peripheral blood lymphocytes in Group E was between Groups C and D.BBB score,pathologic observation and GFAP staining showed a neuroprotective effect of FTY720 and better motor nerve function recovery in Group E than in Groups C and D.Conclusions FTY720 therapy facilitates motor nerve function recovery.Local FTY720 application reduces peripheral blood lymphocytes and lowers the incidence of infection.
. Role of FTY720 therapy in motor nerve function recovery after acute spinal cord injury in rats[J]. CHINESE JOURNAL OF TRAUMA, 2013, 29(10): 1000-1007.
［1］Saganová K,Orendácová J,Sulla I Jr,et al.Effects of long-term FK506 administration on functional and histopathological outcome after spinal cord injury in adult rat.Cell Mol Neurobiol, 2009,29(6-7):1045-1051.
［3］Kowarik MC, Pellkofer HL, Cepok S, et al. Differential effects of fingolimod (FTY720) on immune cells in the CSF and blood of patients with MS. Neurology, 2011, 76(14):1214-1221.
［4］Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. Neurotrauma, 1995, 12(1):1-12.
［6］Jones TB, Hart RP, Popovich PG. Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury. J Neurosci, 2005, 25(28):6576-6583.
［7］Yang L,Blumbergs PC,Jones NR,et al.Early expression and cellular localization of proinflammatory cytokines interleukin - 1 beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury.Spine,2004,29(9):966-971.
［8］Jones TB, Basso DM, Sodhi A, et al. Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci, 2002, 22(7):2690-2700.
［9］Hauben E, Butovsky O, Nevo U, et al. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci, 2000, 20(17):6421-6430.
［10］Fujita T, Inoue K, Yamamoto S, et al. Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot (Tokyo), 1994, 47(2):208-215.
［11］Fujita T, Hirose R, Yoneta M, et al. Potent immunosuppressants, 2-alkyl-2-aminopropane-1, 3-diols. J Med Chem, 1996, 39(22):4451-4459.
［12］Mayer K, Birnbaum F, Reinhard T, et al. FTY720 prolongs clear corneal allograft survival with a differential effect on different lymphocyte populations.Br J Ophthalmol, 2004,88(7):915-919.
［13］Martini S, Peters H, Bhler T, et al. Current perspectives on FTY720. Expert Opin Investig Drugs, 2007, 16(4):505-518.
［14］Vaessen LM, van Besouw NM, Mol WM, et al. FTY720 treatment of kidney transplant patients: a differential effect on B cells,naive T cells,memory T cells and NK cells. Transpl Immunol,2006,15(4):281-288.
［15］Tanaka T,Takahara S,Hatori M,et al.A novel immuno-suppres-sive drug, FTY720, prevents the cancer progression induced by cyclosporine. Cancer Lett, 2002, 181(2):165-171.
［17］Li Q, Li F. Effects of different dose of FTY720 on lymphocyte cell cycle arrest in cardiac transplantation model of rats. Immunopharmacol Immunotoxicol,2010,32(4):680-687.
［18］Lim KG, Tonelli F, Li Z, et al. FTY720 analogues as sphingosine kinase 1 inhibitors: enzyme inhibition kinetics, allosterism, proteasomal degradation, and actin rearrangement in MCF-7 breast cancer cells.J Biol Chem,2011,286(21):18633-18640.
［19］Zhang J, Zhang A, Sun Y, et al. Treatment with immunosuppressants FTY720 and tacrolimus promotes functional recovery after spinal cord injury in rats. Tohoku J Exp Med, 2009, 219(4):295-302.
