辛伐他汀促进脊髓损伤后神经功能修复的实验研究

Therapeutic effect of simvastatin for neurofunction recovery after spinal cord injury in rat

目的:探讨脊髓损伤后急性期应用辛伐他汀对大鼠脊髓神经功能修复的影响。方法:成年雌性SD大鼠32只,假手术组(A组)8只,只做椎板切除,不损伤脊髓,不给药,重物坠落法制作脊髓损伤模型24只,损伤大鼠随机分为三组:羧甲基纤维素钠溶液组(B组)、5mg/kg辛伐他汀治疗组(C组)和10mg/kg辛伐他汀治疗组(D组)(n=8)。术后1d开始灌胃给予辛伐他汀每天一次,连续治疗5周。术后1d、3d以及1～8周,进行BBB评分、斜板试验评价大鼠脊髓神经功能,在第8周时电生理检测大鼠运动及感觉功能的恢复情况,随后处死取材,病理学检查(Luxol fast blue染色)观察残余髓鞘情况。结果:术后2周时,BBB评分D组高于B组(P<0.05);建模3周～8周,BBB评分D组及C组均高于B组(P<0.05),且D组最高(P<0.05)。建模3周时,斜板试验D组及C组均大于B组(P<0.05),且4周～8周,D组角度均大于C组(P<0.05)。感觉诱发电位检查发现,D组,C组的潜伏期小于B组(P<0.05),且D组波幅高于B组(P<0.05)。病理学检查,D组,C组比B组有更多的髓鞘残余(P<0.05)。结论:辛伐他汀急性期治疗脊髓损伤可以促进大鼠损伤脊髓神经功能修复。

Objective：To determine the therapeutic efficacy of simvastatin for neurofunction recovery after acute spinal cord injury（SCI）in rat.Method：spinal cord injury was induced in adult female rats after laminectomy at T9-T10.The SCI animals were randomly divided into 3 groups：sham treated group;5mg/kg and 10mg/kg simvastatin treated group（n=8）.Simvastatin was administered orally at 1 day after SCI and then daily administration for 5 weeks.Locomotor functional recovery was assessed during 8 weeks after operation by performing open-filed locomotor test and inclined-plane test.After that,motor evoked potentials（MEPs）and somatosensory evoked potential（SEPs） were assessed to evaluate the integrity of spinal cord pathways.Then the animals were killed and Luxol fast blue staining was used to assess the content of spared myelin.Result：At 2w after operation,the BBB score in group D was higher than that in group B（P〈0.05）.At 3w,the BBB scores in group D and C were higher than that in group B（P〈0.05）,further,the score in group D was higher that in group C（P〈0.05）.At 3w after operation,the inclined plate angles in group D and C were higher than that in group B（P〈0.05）,further,at 4w,5w,7w and 8w,the angles in group D were higher than those in group C（P〈0.05）.As for the sensory evoked potential,the latency in group D and C were lower than that in group B（P〈0.05）,further,the latency in group D was more lower than that in group C（P〈0.05）;The amplitude in group D was higher than that of B group（P〈0.05）.For the motor evoked potential,the latency in groupD and C were lower than that in group B（P〈0.05）,further,the amplitude in group D was more higher than that in group C（P〈0.05）.For the pathological,group D and C had more myeling pared than group B（P〈0.05）.Conclusion：Acute administration of Simvastatin can improve neurofunction recovery after SCI