一种大鼠脊髓爆炸损伤模型的建立及致伤机制的初步研究

发布时间：2018-06-13 01:09

本文选题：脊髓爆炸损伤 + 动物模型　；参考：《第三军医大学》2015年硕士论文

【摘要】：对临床医生来讲,脊髓损伤的救治一直充满挑战。脊髓损伤不仅给患者带来巨大痛苦,而且也给社会福利造成严重影响。随着局部战争、恐怖主义以及自杀性爆炸袭击的增多,因爆炸导致的脊髓损伤患者也越来越多,因此脊髓爆炸损伤成为科学界关注的焦点。不幸的是目前关于脊髓爆炸伤的研究非常少,脊髓爆炸损伤的病理过程仍然不清楚,并且关于脊髓爆炸损伤的动物模型仍然很少,因此有必要建立一种动物脊髓爆炸损伤模型,不仅可以更好理解脊髓损伤后的病理过程同时也为临床治疗提供了一种新的脊髓损伤研究模型。目的：第一,建立一种可靠、稳定的大鼠脊髓爆炸损伤模型装置,在所建立的装置基础上利用纸质电雷管爆炸产生冲击波,模拟冲击波导致的脊髓损伤。第二,建立大鼠不同程度的脊髓爆炸损伤。第三,初步探讨大鼠脊髓爆炸损伤的机制。方法：研发一种大鼠脊髓爆炸损伤装置,利用800mg TNT作为爆炸源进行爆炸实验。根据爆炸冲击波特征将96只雄性SD大鼠(体重在250-300g之间)被随机分为5组：其中4cm组(n=12只)、5cm组(n=26只)、7.5cm(n=26只)、10cm组(n=26只)和对照组(n=6只)进行试验,通过测量不同爆炸距离下爆炸冲击波的超压峰值,观察不同爆炸距离下大鼠的临床表现,行为学和组织病理学改变对模型进行评估。结果：(1)利用800mgTNT作为爆炸源时,5cm爆炸冲击波超压峰值为998.68KPa,7.5cm为682.54KPa,10cm为245.90KPa。(2)不同爆炸距离下大鼠出现不同程度的临床症状,所有实验组动物中均出现不同程度的呼吸暂停,其中5cm组和7.5cm组动物还出现肢体抽搐和鼻出血症状,距离越近动物的症状越重。(3)不同爆炸距离导致BBB评分差异显著,其中5cm组所有动物均出现持久的截瘫,尽管伤后7d,BBB评分仅为8-9分；7.5cm组伤后一天评分为12-13分,7d为21分；10cm组大鼠伤后1d评分已达21分。此外,和对照组相比,5cm组大鼠和7.5cm组大鼠在伤后3d均有不同程度的运动功能障碍,表现为同侧前肢步长和运动速度显著降低(P0.05),10cm组大鼠与对照组相比无统计学差异(P0.05)。(4)HE染色和Nissl's染色均发现不同爆炸距离导致了不同程度的脊髓损伤,所有实验组的神经元和尼氏体数量均显著降低,爆炸7天后5cm组脊髓前角己无神经元存活,7.5cm组神经元数量明显减少并出现坏死和凋亡现象。大鼠脊髓爆炸损伤后大鼠运动功能的改变与脊髓前角运动神经元的减少直接相关,爆炸距离越近,大鼠运动功能越差,脊髓前角运动神经元的数量越少。值得注意的是,10cm组动物中,虽无临床症状和运动功能障碍,但是脊髓前角神经元形态仍然有改变,尼氏体数量仍然比对照组偏少。结论：(1)我们团队建立的大鼠脊髓损伤模型可靠,重复性及稳定性良好,并且克服了其他模型的一些缺点。(2)该装置能够模拟冲击波产生并且我们成功建立了三种不同程度的脊髓爆炸损伤即5cm组、7.5cm组和10cm组。(3)我们的研究表明脊髓爆炸损伤后大鼠运动功能的改变与脊髓前角运动神经元的减少直接相关,前角运动神经元的数量越少,运动功能的受损越重。
[Abstract]:The treatment of spinal cord injuries has been challenging for clinicians. Spinal cord injury not only brings great pain to the patients, but also has a serious impact on social welfare. With the increase of local wars, terrorism and suicide bombings, more and more patients with spinal cord injury caused by the explosion are damaged, so the spinal cord explosion damage is caused. Unfortunately, there are few studies on the spinal cord injury, and the pathological process of the spinal cord explosion is still unclear, and there are still few animal models about the injury of the spinal cord. Therefore, it is necessary to establish an animal model of the injury of the spinal cord, which can not only better understand the pathology of the spinal cord injury. The process also provides a new model for the study of spinal cord injury for clinical treatment. Objective: first, establish a reliable and stable model device for the spinal cord explosion injury in rats. On the basis of the established device, the shock wave produced by the explosion of the paper electric detonator is used to simulate the injury of the spinal cord caused by the shock wave. Second Third, preliminary study on the mechanism of spinal cord explosion injury in rats. Methods: developing a rat spinal cord explosion damage device, using 800mg TNT as an explosion source to carry out the explosion experiment. According to the Potter sign of explosion shock, 96 male SD rats (between 250-300g) were randomly divided into 5 groups: 4cm group (n=12 only), 5cm Group (n=26 only), 7.5cm (n=26), 10cm group (n=26 only) and control group (n=6 only) were tested by measuring the overpressure peak of explosion shock wave at different explosion distances and observing the clinical manifestations of rats at different explosive distances. The behavior and histopathological changes were evaluated. Results: (1) 5cm explosions when 800mgTNT was used as the source of explosion. The peak overpressure of the shock wave was 998.68KPa, 7.5cm was 682.54KPa, and 10cm was 245.90KPa. (2) with different levels of clinical symptoms. All the animals in the experimental group had different degrees of apnea, of which the animals in the 5cm group and the 7.5cm group also had the symptoms of limb spasm and nosebleed, and the closer the distance to the animals, the heavier the symptoms of the animals. (3 The difference of BBB score was significant in different explosions, among which all animals in group 5cm had persistent paraplegia, although the score of BBB after injury was only 8-9 points, the score of 7.5cm in group 7.5cm was 12-13, 7d was 21, and 1D score of group 10cm was 21. Moreover, compared with the control group, both 5cm group rats and 7.5cm rats were all 3D after injury. Different degrees of motor dysfunction showed a significant decrease in the pace and speed of the ipsilateral forelimb (P0.05). There was no statistical difference between the 10cm group and the control group (P0.05). (4) both HE staining and Nissl's staining found that different distances caused different degrees of spinal cord injury, and the number of neurons and Nissl body in all the experimental groups was significant. After 7 days of explosion, the spinal cord anterior horn of group 5cm had no neuron survival, and the number of neurons in group 7.5cm decreased obviously and appeared necrosis and apoptosis. The change of motor function in rats after the spinal cord explosion injury was directly related to the reduction of motor neurons in the anterior horn of the spinal cord, the closer the distance of the explosion, the worse the motor function of rats, the motion deity of the spinal anterior horn of the rat. It is worth noting that in the 10cm group, although there is no clinical symptoms and motor dysfunction, the neurons in the anterior horn of the spinal cord still change, and the number of Nissl body is still less than that of the control group. Conclusion: (1) the model of spinal cord injury established by our team is reliable, repeatable and stable, and overcame it. Some shortcomings of his model. (2) the device can simulate shock waves and we have successfully established three different levels of spinal cord explosion injury, group 5cm, 7.5cm and 10cm. (3) our study showed that the changes of motor function in rats after spinal cord explosion injury were directly related to the reduction of motor neurons in the anterior horn of the spinal cord. The less the number of the elements, the more the damage to the motor function.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R651.2

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