摘要
目的探究缓释音猬因子(sonic hedgehog,Shh)的聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米微球对大鼠脊髓损伤的修复效果。方法制备PLGA-Shh纳米微球并检测其形态和释放,将36只雌性SD大鼠随机分为假手术(Sham)组、脊髓损伤(SCI)组、PLGA-Shh组。制作SCI模型,PLGA-Shh组大鼠立即在损伤区注射PLGA-Shh微球。术后对大鼠进行旷场实验及BBB评分。分别在术后4和8周取材,Nissl染色观察损伤区吻侧和尾侧脊髓前角运动神经元的变化;采用免疫组织化学染色观察损伤区吻侧和尾侧神经元标记物NeuN表达情况。结果PLGA-Shh组大鼠术后第7周、第8周BBB评分、旷场总移动距离均高于SCI组(P均<0.05);Nissl染色结果显示,术后8周PLGA-Shh组大鼠脊髓损伤区吻侧和尾侧脊髓前角运动神经元数量高于SCI组(P均<0.05);免疫组织化学染色结果显示,术后8周PLGA-Shh组大鼠脊髓损伤区吻侧和尾侧NeuN表达高于SCI组(P均<0.05)。结论包载Shh的PLGA纳米微球可持续释放Shh,PLGAShh纳米微球对大鼠脊髓损伤有修复作用,并可改善大鼠后肢运动功能。
Objective To investigate the repair effect of poly(lactic-co-glycolic acid,PLGA)nanospheres of sustained-release of sonic hedgehog(Shh)on spinal cord injury(SCI)in rats.Methods PLGA nanospheres of sustained-release of Shh were prepared,and their morphology were observed and the release conditions were detected.Thirty-six female SD rats were randomly assigned to three groups:Sham group,SCI group,and PLGA-Shh transplantation group.The SCI rat model was established,and the PLGA-Shh transplantation group was injected with sustained-release nanospheres immediately.After the operation,open field test and BBB scoring were conducted for rats.The tissues of each group were taken at 4 weeks and 8 weeks after surgery.The motor neurons(MNs)in the anterior horn of the rostral and caudal side of SCI region were observed by Nissl staining,and the expressions of neuron-specific nuclear protein(Neu N)in the rostral and caudal side of SCI region were observed by immunohistochemical staining.Results The BBB scores and the total moving distance in the open field at 7 weeks and 8 weeks post-injury in the PLGA-Shh group were higher than those in the SCI group(P all<0.05).The Nisslstainingresults showed that after 8 weeks post-injury,the number of MNs in the anterior horn of the rostral and caudal side of SCI region of the PLGA-Shh group was higher than that in the SCI group(P all<0.05).The immunohistochemical staining results showed that after 8 weeks post-injury,the expressions of Neu N on the rostral and caudal side of SCI region of PLGA-Shh group were higher than those in the SCI group(P all<0.05).Conclusion PLGA nanospheres encapsulated with Shh factor have sustained release properties,which has the repair effect on SCI in rats,and can also improve the hind limb motor function of SCI rats.
作者
夏宇
孙佳
齐争艳
马琳
牛建国
文玉军
XIA Yu;SUN Jia;QI Zhengyan;MA Lin;NIU Jianguo;WEN Yujun(Department of Human Anatomy and Histology Embryology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;Ningxia Key Laboratory of Cerebrocranial Diseases,Ningxia Medical University,Yinchuan 750004,China)
出处
《宁夏医科大学学报》
2022年第7期677-681,695,共6页
Journal of Ningxia Medical University
基金
国家自然科学基金项目(81660216)
宁夏自然科学基金项目(2020AAC03182)
宁夏重点研发计划项目(2021BEG03096)。
