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目的 为了研究肌萎缩侧索硬化症致病机理和药物研发,建立第4腰椎腹侧神经根牵拉大鼠模型,并用脑源性神经营养因子作为阳性药物进行模型的有效性验证。方法 首先对5只SD雄性大鼠进行手术,一周后用抗胆碱乙酰转移酶抗体进行免疫组织化学染色观察脊髓前角运动神经元数量的变化;预实验证明手术模型成功后,将40只7周龄SD雄性大鼠随机分为四组,两组模型对照组及两个脑源性神经营养因子治疗组(手术后立刻预防性给药组和手术后一周治疗性给药组)。使用抗胆碱乙酰转移酶免疫组织化学染色观察运动神经元数量的变化。结果 大鼠手术后恢复良好,临床观察无异常。染色结果证明手术牵拉后,造成明显的脊髓前角运动神经元变性死亡。与对照组相比,用脑源性神经营养因子治疗的神经根牵拉动物,不管是预防性给药还是手术1周后再进行治疗性给药都达到了良好的治疗效果,胆碱乙酰转移酶染色阳性神经元细胞数量显著增加(P<0.0001),结果分别为17.85%比93.06%;26.6%比87.27%。结论 成功的建立大鼠第4腰椎腹侧神经根牵拉模型,为肌萎缩侧索硬化症的研究提供了一种有价值的动物模型。
Objective To study the pathogenesis and drug development of amyotrophic lateral sclerosis (ALS), establish the fourth lumbar ventral nerve root traction rat model and use BDNF as a positive drug to validate the model. Methods Five male Sprague-Dawley rats were operated on. One week later, the number of motoneurons in the anterior horn of spinal cord was observed by immunohistochemical staining with anticholinergic acetyltransferase. After the successful operation, 40 7 Male Sprague-Dawley (SD) male rats were randomly divided into four groups, two model control groups and two brain-derived neurotrophic factor treatment groups (prophylactic group and postoperative week-long therapeutic group). The changes of motor neurons were observed by using anticholinergic acetyltransferase immunohistochemical staining. Results After operation, the rats recovered well and no abnormality was observed in the clinical observation. Dyeing results show that after surgical traction, causing significant degeneration of spinal motor neurons anterior horn death. Compared with the control group, the nerve root traction neurons treated with BDNF achieved good therapeutic effect either for prophylactic administration or for one week after operation, and choline acetyltransferase The number of neuron-positive neurons increased significantly (P <0.0001), the results were 17.85% vs 93.06%, 26.6% vs 87.27% respectively. Conclusion Successful establishment of the fourth lumbar rat ventral nerve root traction model provides a valuable animal model for the study of amyotrophic lateral sclerosis.