Nutlin-3a缓释微球促大鼠脊髓损伤后功能恢复的实验研究

发布时间：2018-03-13 19:30

本文选题：脊髓损伤　切入点：微球　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:探讨Nutlin-3a-PLGA微球对大鼠脊髓损伤后运动功能恢复的影响。方法:采用单乳化法制备Nutlin-3a-PLGA微球。健康雌性成年SD大鼠采用随机数字表法分为单纯损伤组、生理盐水微球治疗组和Nutlin-3a-PLGA微球治疗组,每组12只,并对T10脊髓进行右半横断损伤;另取3只大鼠进行正常铬化青染色。单纯损伤组仅行脊髓右半横断损伤而不给予治疗,生理盐水微球治疗组术后予以生理盐水微球治疗,Nutlin-3a-PLGA微球治疗组术后予以Nutlin-3a-PLGA微球治疗。术后2、4周行铬化青染色观察脊髓脱髓鞘情况,术前1天,术后2、3、4周行Catwalk步态分析正常步序比、站立时间、足印平均强度、两后爪脚间距离以及相对足印距离5个时间-空间参数评价大鼠运动功能变化。结果:伤后4周与单纯损伤组和生理盐水微球治疗组比较,Nutlin-3a-PLGA微球治疗组铬化青染色显示脱髓鞘病变较轻,髓鞘排列较为紧密。与术前比较,术后2周单纯损伤组和生理盐水微球治疗组Catwalk步态分析各项行为学参数差异有统计学意义;Nutlin-3a-PLGA微球治疗组正常步序比、两后爪脚间距离以及左、右相对足印距离差异有统计学意义,左后肢站立时间和前肢足印平均强度差异无统计学意义。与单纯损伤组和生理盐水微球治疗组比较,Nutlin-3a-PLGA微球治疗组伤后2周左后肢站立时间和前肢足印平均强度均降低,正常步序比增加;伤后4周两后爪脚间距离减小,左、右相对足印距离显著减小。结论:Nutlin-3a-PLGA微球局部作用能够促进脊髓半横断损伤大鼠运动功能的恢复,对损伤节段轴突的再生可能有促进作用。
[Abstract]:Objective: to investigate the effect of Nutlin-3a-PLGA microspheres on motor function recovery after spinal cord injury in rats. Methods: Nutlin-3a-PLGA microspheres were prepared by single emulsification. Normal saline microspheres treatment group and Nutlin-3a-PLGA microsphere treatment group, each group, 12 rats, and T10 spinal cord right half transection injury, another 3 rats were taken for normal chromocystin staining. The simple injury group only right half spinal cord transection injury without treatment, The saline microspheres group was treated with Nutlin-3a-PLGA microspheres after operation, and the Nutlin-3a-PLGA microspheres were treated with Nutlin-3a-PLGA microspheres. Catwalk gait analysis was performed at 2 ~ 3 ~ 4 weeks postoperatively. The normal step order ratio, standing time, and the average strength of footprints were analyzed. Results: the changes of motor function in rats were evaluated by 5 time and space parameters of the distance between the feet of the two posterior claws and the relative footprint distance. Results: Nutlin-3a-PLGA microsphere treatment group was compared with the simple injury group and the saline microsphere treatment group at 4 weeks after the injury and the chrominated blue staining was compared with that in the Nutlin-3a-PLGA microsphere treatment group. Color showed that demyelinating lesions were mild. Compared with before operation, there were significant differences in Catwalk gait analysis between simple injury group and saline microsphere treatment group 2 weeks after operation. There were significant differences in normal step ratio, distance between two posterior claws and feet, left, left, and so on in Nutlin-3a-PLGA microsphere treatment group. The difference of right relative footprint distance is statistically significant. There was no significant difference in the standing time of left hind limb and the average strength of forefoot imprint. Compared with the simple injury group and the saline microsphere treatment group, the standing time of left hind limb and the average strength of forefoot imprint decreased in the Nutlin-3a-PLGA microsphere treatment group 2 weeks after injury. The normal step sequence ratio increased, the distance between the two paws and feet decreased, and the distance between left and right foot marks decreased significantly 4 weeks after injury. Conclusion the local action of the microspheres at 1: Nutlin-3a-PLGA can promote the recovery of motor function in rats with spinal cord hemitranverse injury. It may promote the regeneration of injured segmental axons.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.2

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