[1]覃小霞,刘文雪,罗泽汝心,等.Nutlin-3a-PLGA微球促大鼠脊髓损伤后的运动功能恢复[J].第三军医大学学报,2017,39(18):1816-1823.
 QIN Xiaoxia,LIU Wenxue,LUO-ZE Ruxin,et al.Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury[J].J Third Mil Med Univ,2017,39(18):1816-1823.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第18期
页码:
1816-1823
栏目:
基础医学
出版日期:
2017-09-30

文章信息/Info

Title:
Nutlin-3a-PLGA microspheres promote motor function recovery in rats after spinal cord injury
作者:
覃小霞刘文雪罗泽汝心伍亚民王志刚吴宗辉虞乐
重庆医科大学附属第二医院:康复医学科,超声影像学研究所;黔南民族职业技术学院,计算机科学系;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;西南大学医院
Author(s):
QIN Xiaoxia LIU Wenxue LUO-ZE Ruxin WU Yamin WANG Zhigang WU Zonghui YU Lehua

Department of Rehabilitation Medicine, 4Institute of Ultrasound Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010; 2Faculty of Computer Sscience, Qiannan Polytechnic for Nationalities, Qiannan Buyi and Miao Autonomous Prefecture, Guizhou Province, 558022; 3State Key Laboratory of Trauma, Burns and Combined Injury, Department 3, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042; 5Southwest University Hospital, Chongqing 400715, China

关键词:
脊髓损伤微球行为学评价步态分析
Keywords:
spinal cord injury microspheres behavior evaluation gait analysis
分类号:
R452;R493;R651.205
文献标志码:
A
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T10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(P<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(P<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(P<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(P>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(P<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(P<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 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 T10 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, P<0.05) and the negative control group (1 347.33±114.42, P<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 (P<0.05). But for the treatment group, notable differences were found in regularity index, hindlimb base of support and ipsilateral relative distance (P<0.05), though not in left hindlimb standing time and forelimb mean intensity (P>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 (P<005). 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 (P<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 (P<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.
 

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更新日期/Last Update: 2017-09-29