咯利普兰对大鼠脊髓损伤后保护作用及其机制

目的探讨咯利普兰对大鼠脊髓损伤(SCI)后的保护作用及其可能机制。方法将84只SD大鼠随机分为三组:假手术组(n=4)、损伤组(n=40)和治疗组(n=40)。大鼠SCI模型采用纽约大学脊髓重物坠落伤模型。治疗组伤后即刻腹腔内注射咯利普兰,剂量为0.5 mg(/kg.d),2次/d,连续3d。损伤前后对损伤组和治疗组大鼠进行开放场地试验(BBB)评估大鼠脊髓功能。免疫组化染色分析三组大鼠损伤前后脊髓兴奋性氨基酸转运蛋白4(EAAT4)表达情况。结果损伤组和治疗组伤后即刻大鼠BBB评分均为0,处于完全瘫痪状态;然后BBB评分逐渐增高;伤后42、56和64d,治疗组BBB评分明显高于损伤组(P<0.01)。假手术组脊髓组织形态正常,EAAT4表达较少;脊髓损伤1周后,损伤中央出现较大空洞,EAAT4表达明显升高;而治疗组,组织空洞缩小,EAAT4表达较损伤组明显增加。结论咯利普兰有助于大鼠脊髓损伤后功能恢复,其机制可能与增加EAAT4表达有关。

Effects of rolipram on expression of excitatory amino acid transporter 4 in injured spinal cords of the rats

Objective To investigate the protective effect of rolipram on the injured spinal cords and its mechanism in rats.Methods Eighty-four adult female Sprague-Dawley(SD) rats weighing 250～300 g were randomly divided into 3 group,i.e.sham injury group,control group and rolipram treatment group.Spinal cord injury(SCI) model was made by New York University impactor.Rolipram(0.5 mg/kg/day) was intraperitoneally injected twice a day after SCI for 3 day in the rolipram treatment group.The expression of excitatory amino acid transporter 4(EAAT4) was determined in the spinal cords of all the groups by immunohistochemical technique.The behavior function was examined by Basso,Beattie and Bresneban open filed locomotor test(BBB) in all the groups.Results The level of EAAT4 expression was significantly higher in rolipram treatment group than that in the control group,which was significantly higher than that in the sham group a week after the injury.BBB scores were zero immediatelly after SCI in both the control and tretment groups and then they began gradually rising.BBB scores were significantly higher in rolipram treatment group than those in the control group 42,56 and 64 days after the injury(P<0.01).ConclusionsRolipram may promote rehabilitation of the behavior function in the rats with SCI by the increase in the expression level of EAAT4,which can decrease the toxic effect of excitatory amino acid on the spinal cord neurons.