Abstract: Objective： To observe the effect of delayed administration of etanercept on the motor function, the expression of apoptosis-related genes and the pathological alterations of spinal cord in vivo in experimental murine model of spinal cord injury (SCI). Methods: Seventy-two male adult SD rats were randomly divided into 6 groups, which were subjected to SCI induced by the application of vascular clips (force of 70 g) to the dura. Experimental groups (E1, E2, and E3 group) were given administration of etanercept immediately, 1 h, and 8 h after SCI. The control groups (C1, C2, and C3 group) were given administration of saline at the same time as experimental groups. Six rats of each group were killed 24 h  after SCI in order to collect the samples for testing the expression of Bax and Bcl-2 by Western blot. The rest were killed 14 d after SCI for observing the pathological alteration using light microscopy. The recovery of motor function was graded using the modified murine Basso, Beattle, and Bresnahan (BBB). Results: (1) The results of the expressions of Bax and Bcl-2 by Western blot: the gray value of the expression of Bax of E1 group was 165.423±2.946, of E2 group 135.391±3.045, of E3 group 108.543± 6.999, and of the control group 69.054±0.774, and the gray value of the expression of Bcl-2 of E1 group was 58.854±3.592, of E2 group 84.315±2.138, of E3 group 125.091±2.699, and of the control group 156.304±2.490. (2) The results of BBB score: etanercept given immediately or 1 h after SCI could improve the recovery of the rats. There were significant differences in BBB score 14 d after SCI between E1 group (13.000±1.095) and C1 group (7.167±0.753), E2 group (9.833±1.472) and C2 group (7.000±0.632)  while there were no significant difference between E3 group (7.333±0.516) and C3 group (6.833±0.753). (3) The result of histological alteration: histological alterations, such as necrosis, infiltration of lymphocytes and fibroblast and loss of nerve cells, were found attenuated in  E1 and E2 groups, compared with C1 and C2 groups. There was no obvious difference between E3 and C3 groups.  Conclusion: Administration of etanercept may inhibit the apoptosis after SCI, but this kind of effect may be too weak to improve the BBB score and histological alterations obviously when administration of etanercept is delayed 8 h after SCI. The clinical value of etanercept to SCI needs to be further validated.

Key words: TNFR-Fc fusion protein, Spinal cord injuries, Medication systems, Treatment outcome