Effect Of Infliximab Combinated With Methylpredni-Solone On Expression Of TNF-a、Caspase-3in A Rat Model Of Acute Spinal Cord Injury

Objective:Establish rat model of acute spinal cord injury and Investigate the effects of methyl prednisolone (MP), infliximab, and the combination of these two agents on expression of TNF-a(Tumor necrosis factor a), caspase-3(cysteine protease-3) in a rat model of acute spinal cord injury(ASCI), confirm the therapeutic efficacy of infliximab combinated with methylprednisolone(MP) in the treatment of rat spinal cord injury.Method:90adult male Sprague Dawley rats with300-350g body weight were randomly distributed into six groups as follows:A. normal control group(Group NC, n=15);B.sham-operation group(Group SO, n=15. C.SCI+placebo group(Group NS, n=15); D.SCI+MP group (Group MP, n=15);E.SCI+infliximab group(Group IN, n=15); F.SCI+Infliximab+MP group(Group I+M). Allen’s weight drop method was used to establish the rat model of acute spinal cord injury at T10section., sham-operation group only received laminectomy operation and intraperitoneal injection lml NS、normal control group do nothing.2ml drug was experimental injected after spinal cord injury:Each dose of intraperitoneal injection (methylprednisolone30mg/kg, infliximab5mg/kg, Group C use NS). In the research we applied BBB locomotor rating scale to assess the hindlimb motor functional score for5rat model of ASCI after the model was established in each group. We collect the spinal cord tissue samples from the injured segment at the time point of24th hours after SCI from other rat models of ASCI in each group and5samples of which in each group were prepared for immunohisto-chem istry staining to assay the expression of TNF-α、caspase-3and other5samples in each group were used to evaluate the expression of TNF-a mRNA、caspase-3mRNA.Result:(1)BBB motor function score assessment:The BBB score of the model groups was dropped quickly after acute spinal cord injury,but then gradually increased in the treatment groups. The score of at14th,21th days after ASCI, group MP、group IN、group I+M was significantly higher than other groups (p<0.05); moreover, the score of group I+M was significantly higher than only use MP and IN group (p<0.05)(2) Immunohistochemistry and RT-PCR assessment:at the time point of24th hour after ASCI,The amounts of TNF-α、caspase-3positive cell and the expression level of TNF-a mRNA、caspase-3mRNA in Group MP、group IN and Group I+M were less than other Groups (p<0.05); moreover, the positive cells and the expression level were significantly lower than only use MP and IN group (p<0.05)Conclusion:(1) Both infliximab and methylprednisolone can Suppressed the expression of TNF-α、caspase-3in the rat acute spinal cord injury model. The two agents can mitigate the severity and improve the locomotor function in rat ASCI model.(2) Infliximab combinated with methylprednisolone exhibit more powerful ability to reduce the expression of TNF-α、caspase-3in rat ASCI model, moreover, The combined treatment of acute spinal cord injury better than the separate use.