Effect of cyclosporine A on the expression of cycloxygenase-2 and tumor necrosis factor-α in early stage of spinal cord injury in rat

English Keywords:Spinal cord injury  Cyclosporin A  Cycloxygenase-2  Tumor necrosis factor-α  Rat

English Abstract:

  【Abstract】 Objective：To investigate the effect of the cyclosporine A（CsA） on the expression of cycloxygenase-2（Cox-2） and tumor necrosis factor-α（TNF-α） in acute spinal cord injury，and the mechanism of CsA on spinal cord injury in rat.Method：180 rats were randomly divided into control group，injury group and the CsA-intervention group with 60 rats in each group.An impact of 2.5g·cm was used to induce spinal cord injury in rat both in injury group and in intervention group.In CsA-intervention group，CsA（2.5mg/kg） was administrated in rats through caudal vein injection 1h after injury，then repeated per 12h after injury，while the control group and injury group received the same dose of normal saline at the same time point.The injured spinal cord segment was collected and processed pathologically at 2h，6h，12h，24h，4h8 and 72h after operation.HE staining and immunohistochemistry staining（TNF-α by the EnVision detection system and Cox-2 by the SP detection system） were performed for every specimen.The expressions of Cox-2 and TNF-α were analyzed quantitatively by HPIAS-2000 high-resolution color graphic pathology report management system.Result：HE staining showed normal of rat spinal cord in control group without bleeding and necrosis.Edema and hemorrhage instead of necrosis in spinal cord gray matter cauld be seen in 2h，6h after injury both in injury group and in intervention group.A wide range of focal hemorrhage and formation of cysts after bleeding occurred in 12h or 24h after injury in spinal cord gray matter.Neurons appeared as swelling，part of nucleus concentrated，HE staining increased，numerous red blood cells and myelin slight swelling were seen in the white matter as well.Neurons appeared pyknosis，necrosis，dissolution in 48h or 72h after injury in the spinal cord gray matter.Microglial cell proliferation and neutrophil infiltration were evidenced in the injured spinal cord.Numerous red blood cells and myelin swelling were seen in the white matter.A great quantity of emptiness，inflammation cell infiltration and microglial cell proliferation were evidenced.Pathological severity at any time point in intervention group was milder than injury group.The expression of Cox-2 remained uncertainty in control group and reached peak at 6h after injury，then decreased.Cox-2 expression in injury group in 72h was higher than control group（P<0.05），while was equal to intervention group in 48h after injury（P> 0.05），Cox-2 expression in intervention group was lower than injury group at each time point（P<0.05）.The expression of TNF-α remained uncertainty in control group.The expression of TNF-α was detected 2h after injury in injury group and the intervention group，which reached peak at 12h after injury，then decreased.The expression of TNF-α in injury group was higher than control group（P<0.05） in 72h after injury.The expression of TNF-α in intervention group resumed to the baseline level of the control group（P>0.05） 72h after injury.TNF-α expression in intervention group was lower than injury group at each time point（P<0.05）.Conclusion：CsA down-regulate the expression of Cox-2 and TNF-α significantly in SCI rats，which can alleviate the secondary spinal cord injury.