Effect Of Cyclosporine A On The Expression Of Cox-2 And TNF-α In The Early Period Of Rat Spinal Cord Injury

Objective: To investigate the inchoate protection and the therapeutic mechanism of cyclosporine A on the acute spinal cord injury.Methods: An experimental rat model of spinal cord injury was established. 180 rats were randomly divided into the control group, the injury group and the CsA-treated after injury group, 60 rats respectively. Rats were anesthetize, sacrificed and intubated for reperfusion at different time points after modeling. The injury segmental spinal cord was isolated, fixed overnight, embedded and sliced. The structure of the rat spinal cord was shown by HE staining. The expression of Cox-2 and TNF-a in the rat spinal cord were detected by immunohistochemistry staining (TNF-a by the EnVision Detection System and Cox-2 by the SP Detection System). The expressions of Cox-2 and TNF-a were analyzed quantitatively by HPIAS-2000 high-resolution color graphic pathology report management system.Results: 1. HE staining showed white matter, gray matter, the anterior horn and the posterior horn in the normal rat spinal cord. Blooding, but without necrosis was shown in the injury rat spinal cord and CsA treated after injury rat spinal cord within 6h after injury. Widespread blooding and capsular space formed after blooding, neuronal degeneration and necrosis, gitter cell proliferation and neutrophil infiltration were showed in the injury rat spinal cord subsequently. Local blooding, some neuronal degeneration and necrosis were showed in the CsA treated after injury rat spinal cord subsequently. However, blooding, neuronal degeneration and necrosis, gitter cell proliferation and neutrophil infiltration in the CsA treated after injury rat spinal cord were less than that in the injury rat spinal cord.2. For Cox-2, suspicious expression was shown in normal rat spinal cord, strong expression in injury rats spinal cord and weak expression in CsA treated after injury rats spinal cord. The expression of Cox-2 could be detected 2h after injury in the injury group and the CsA treated after injury group. The expression of Cox-2 reached its peak at 6h after injury, but lasted only for a short duration. The expression of Cox-2 approached the baseline levels at 48h after injure and was close to the baseline level at 72h after injury. The differences among the three groups at different time point were statistical significance (2h: F=179.670, P<0.001; 6h: F=337.489, P<0.001; 12h: F=393.312, P<0.001; 24h: F=197.541, P<0.001; 48h: F=35.174, P<0.001; 72h: F=3.995, P=0.030). 3. For TNF-a, suspicious expression or weak expression was shown in normal rat spinal cord, strong expression in injury rats spinal cord and middling expression in CsA treated after injury rats spinal cord. The expression of TNF-a could be detected 2h after injury in the injury group and the CsA treated after injury group. The expression of TNF-a reached its peak at 12h after injury, but lasted only for a short duration. The expression of TNF-a was close to the baseline level at 72h after injury. The differences among the three groups at different time point were statistical significance (2h: F=300.328, P<0.001; 6h: F=1856.199, P<0.001; 12h: F=3710.988, P<0.001; 24h: F=2516.988, P<0.001; 48h: F=647.982, P<0.001; 72h: F=3.454, P=0.046).Conclusions: CsA depresses significantly the expression of Cox-2 and TNF-a in the rat spinal cord after injury and relieves the secondary spinal cord injury. CsA may be a new treatment for the secondary spinal cord injury.