The Study of the Influence of BMS-345541 on Motor Function of Hind Limbs and the Infiltrating Leukocytes after Spinal Cord Injury in Rats
|School||Dalian Medical University|
|Keywords||Spinal cord injury NF-κB BMS-345541 BBB points|
Objective:To investigate the influence of subdural injection of BMS-345541 on motor function of hind limbs and the infiltrating leukocytes after early acute spinal cord injury(ASCI) in rats models.Materials and Methods:1. 60 health mature female SD rats(200-220 mg) were divided into three groups, the rats of group A(sham-operated group)were accepted T12 laminectomy and soft tissues and skins were directly sutured after exposure, and SCI was induced after laminectomy by modified Allen’s Weight Drop in the other two groups;the rats of group B(blank group)were accepted with subdural injection of 10μl 1% DMSO;the rats of group C(therapy group)were accepted with subdural injection of 10μl BMS-345541.The injuryed animals were sacrificed at 24th hr,and then,the injuried spinal cord tissues were achieved and prepared for Western blot analysis and myeloperoxidase (MPO) activity assay.Functional recovery were observed in 1st,3rd,7th and 14th days after surgery.2. The changes of hindlimb locomotor functional recovery of rats were assessed in open field according to BBB score method.3. Expression of NF-κB p65 and ICAM-1 in each group after SCI at 24th hr were observed by Western blot,using image analysis system to calculate the IOD value of each sample.4. The protein samples after SCI at 24th hr were observed by ultraviolet-visible spectrophotometer. Use the formula to calculate the MPO value with the OD value in each group.5. Statistical analysis:Data are expressed as mean±standard error,use SPSS 13.0 software pckage for single-factor analysis,and differences were considered statistically at P <0.05 level.Results:1. Locomotor function of group B and C were gradually recovered after spinal cord contusion. From the 7th day, scores in group C were more significantly increased than those of group B,the differences were statistically significant (P <0.05).2. The expression of NF-κB p65 and ICAM-1 were detected with western blot analysis in each group. The expression of NF-κB p65 and ICAM-1 were maintain a low expression state in group A, but the expression in group B were increased obviously. And the expression level in group C were significantly lower than those in group B ,and statistical significance was found (P <0.05).3. The value of MPO in the rats of group C treated with BMS-345541 were significantly lower than those in group B at 24h after injury, but higher than those in group A, statistical significance was found (P <0.05).Conclusions:1. BMS-345541 can improves the functional recovery after SCI in rats.2. BMS-345541 can blockade of SCI-induced NF-κB p65 activity decreases injuryed cord ICAM-1 protein level and the infiltrating leukocytes,accordingly attenuates the inflammatory response in the injured spinal cord tissues in rats.