Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury

Xiaoxia QIN; Wenxue LIU; Ruxin LUO-ZE; Yamin WU; Zhigang WANG; Zonghui WU; Lehua YU

doi:10.16016/j.1000-5404.201703038

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Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury

Basic Medicine | 更新时间：2026-01-09

- Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury
- Journal of Third Military Medical University Vol. 39, Issue 18, Pages: 1816-1823(2017)
- 作者机构：
  
  1.400010 重庆，重庆医科大学附属第二医院：康复医学科
  2.558022 贵州，黔南民族职业技术学院，计算机科学系
  3.400042 重庆，第三军医大学大坪医院野战外科研究所第三研究室，创伤与烧伤国家重点实验室
  4.400010 重庆，超声影像学研究所
  5.400715 重庆，西南大学医院
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201703038
  CLC： R452;R493;R651.205
- Received：07 March 2017，
  
  Revised：2017-04-07，
  
  Published：30 September 2017
- 稿件说明：
移动端阅览
Xiaoxia QIN, Wenxue LIU, Ruxin LUO-ZE, et al. Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury[J]. Journal of Third Military Medical University, 2017, 39(18): 1816-1823.
DOI：

Xiaoxia QIN, Wenxue LIU, Ruxin LUO-ZE, et al. Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury[J]. Journal of Third Military Medical University, 2017, 39(18): 1816-1823. DOI： 10.16016/j.1000-5404.201703038.

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；另取3只大鼠进行正常脊髓铬化青染色。对T

脊髓进行右半横断损伤。单纯损伤组仅行脊髓右半横断损伤而不给予干预，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 d，伤后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（1 461.44±123.46）和生理盐水微球治疗组（1 347.33±114.42）比较，Nutlin-3a-PLGA微球治疗组（1 879.46±115.41）铬花青染色显示脱髓鞘病变较轻（

0.05），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（

0.05）；Nutlin-3a-PLGA微球治疗组正常步序比、两后爪脚间距离以及相对足印距离差异有统计学意义（

0.05），左后肢站立时间和前肢足印平均强度差异无统计学意义（

0.05）。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、左右前肢足印平均强度降低，正常步序比增加；伤后4周单纯损伤组、生理盐水微球治疗组和Nutlin-3a-PLGA微球治疗组两后爪脚间距离分别为3.20±0.89 cm，3.23±0.90 cm，2.29±0.36 cm，Nutlin-3a-PLGA微球治疗组与其余两组比较差异有统计学意义（

0.05）；单纯损伤组、生理盐水微球治疗组和Nutlin-3a-PLGA微球治疗组左侧相对足印距离分别为10.17±6.40 cm、9.75±6.92 cm和2.85±1.72 cm，右侧分别为7.63±4.78 cm、8.21±4.82 cm和3.00±2.07 cm；Nutlin-3a-PLGA微球治疗组与其余两组比较左右两侧相对足印距离差异均有统计学意义（

0.01）。

结论

Nutlin-3a-PLGA微球局部作用能促进脊髓后半损伤大鼠传导功能及运动功能的恢复，对损伤节段轴突的再生可能有促进作用。

Abstract

Objective

To determine 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 〖HJ1.8mm〗emulsion method. A total of 36 healthy SD rats were randomly and equally divided into simple injury group

negative control group (normal saline containing microspheres) and Nutlin-3a-PLGA microspheres treatment group

and another 3 rats were subjected as normal control for spinal cord morphology with eriochrome cyanine staining. Spinal cord injury was inflicted by complete right-hemisection at T

with fine microdissection scissors. Nutlin-3a-PLGA microspheres were then topically delivered to the lesion site in the treatment group

and the negative control group received the same amount of saline-PLGA microspheres. Myelin sheath was observed with eriochrome cyanine staining in 2 and 4 weeks after injury. Catwalk gait analysis system (regularity index

standing time

mean intensity of footprint

hindlimb base of support

and 5 temporal-spatial parameters of ipsilateral relative distance) was applied to describe the behavioral characteristics of the rats in 1 d before and 2

3 and 4 weeks after injury.

Results

In 4 weeks after injury

eriochrome cyanine staining showed demyelinating lesions were significantly milder in the treatment group

with myelination arranged more closely(1 879.46±115.41)

when compared to the simple injury group (1 461.44±123.46

0.05) and the negative control group (1 347.33±114.42

0.05). There were obvious differences in each behavior parameters in the simple injury group and negative control group before and in 2 weeks after injury (

0.05). But for the treatment group

notable differences were found in regularity index

hindlimb base of support and ipsilat

eral relative distance (

0.05)

though not in left hindlimb standing time and forelimb mean intensity (

0.05). When compared with the other 2 groups

the treatment group had significantly decreased left hindlimb standing time

mean intensity of left and right forelimb footprint

and increased regularity index in 2 weeks after injury (

0.05). In 4 weeks after injury

the hindlimb base of support were 3.20±0.89

3.23±0.90

and 2.29±0.36 cm

respectively in the simple injury group

negative control group and treatment group

with significant difference in the latter group and the other 2 groups (

0.05). The left ipsilateral relative distance was 10.17±6.40

9.75±2.85 and 6.92±1.72 cm

respectively

and that of the right side was 7.63±4.78

8.21±4.82 and 3±2.07 cm in the above 3 groups

with those of the treatment group more significant (

0.01).

Conclusion

Nutlin-3a-PLGA microspheres improve conduction function and motor function in rats after spinal cord injury

and they may promote the axonal regeneration of the injured segments.

关键词

Keywords

references

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