尼莫地平对大鼠脊髓损伤的作用研究

目的:研究尼莫地平(nimodipine)对大鼠脊髓损伤后继发性损害的保护作用。方法:成年SpragueDawley雄性大鼠24只,体重180～220 g,采用NYU脊髓撞击伤仪制成脊髓损伤模型后,随机分成尼莫地平(n=12)和生理盐水组(n=12)。两组大鼠受伤后1 h内分别经腹腔给予尼莫地平(1.0 mg/kg)或等量盐水治疗,3次/d,共1周。于受伤后1周和2周进行BBB评分和足迹实验对大鼠双后肢运动功能进行评估。受伤后2周,对损伤部位脊髓组织丙二醛(MDA)含量及脊髓过氧化物酶(MPO)活性进行检测;同时进行免疫组织化学检查确定损伤星形胶质瘢痕和所形成的坏死空洞,利用ED1观察活性小胶质细胞和巨噬细胞。结果:与生理盐水组比较,通过旷场试验(BBB评分)和足迹实验,脊髓损伤后大鼠尼莫地平组1周和2周运动功能明显改善(P<0.01)。与盐水组比较,伤后2周,尼莫地平组大鼠脊髓组织中MDA水平(nmol/g,25.6±9.7 vs 68.5±16.7)和MPO活性(U/g,252.2±63.9 vs 382.8±108.2)均明显降低(P<0.01);尼莫地平组空洞面积(mm2,4.45±1.28 vs 6.16±2.65)和ED1抗体免疫组化染色阳性面积(mm2,1.87±0.42 vs 2.86±1.01)也明显减少(P<0.01)。结论:尼莫地平可以减轻大鼠脊髓损伤后自由基的氧化损伤作用,减小空洞面积和炎症细胞浸润,具有促进脊髓损伤后的修复作用。

Protective effects of nimodipine for spinal cord injury in the rats

Objective: To study protective effect of nimodipine in rats with secondary spinal cord injury(SCI).Methods: The adult Sprague Dawley male rat weight was 180~220 g,spinal cord injury models were made by NYU impact,and randomly divided into nimodipine(n=12) and normal saline group(n=12).One hour after the injury,two group rats were separately treated by the nimodipine(1.0 mg/kg,ip) or equivalent normal saline,three times/d,a total of 1 week.In 1 week and 2 weeks after the injury,BBB scale and footprint test were tested in rats for evaluating hind double movement function.Two weeks after the injury,the area of injury to the spinal cord tissue malondialdehyde(MDA) content and myeloperoxidase(MPO) activity were detected.Simultaneously the damage star glial scar and empty formation of necrosis were determined by immunohistochemical staining of GFAP,and observing activated microglia and macrophages using ED1.Results: Compared with normal saline group,after SCI rat,movement function was obviously improved(P<0.01) at 1 week and 2 weeks in nimodipine-treated group by BBB scale and footprint test.Two weeks after injury,the MDA level(25.6±9.7 nmol/g vs 68.5±16.7 nmol/g) and MPO activity(252.2±63.9 U/g vs 382.8±108.2 U/g) in the spinal cord tissues were reduced significantly(P<0.01),and empty area(4.45±1.28 mm2 vs 6.16±2.65 mm2) and ED1 immunohistochemical positive area(1.87±0.42 mm2 vs 2.86±1.01 mm2) were also significantly reduced(P<0.01) in nimodipine group.Conclusion: Nimodipine can reduce free radical oxidative damage in SCI model,reduce the empty area and inflammatory cells infiltrating,and have promotion effecton SCI repair function.