PLGA引导转NT-3基因小胶质细胞对损伤脊髓功能恢复的影响  

THE INFLUENCE OF ACTIVATED TRANSGENIC MICROGLIA WITH PLGA ON RECOVERY OF NERVE FUNCTION AFTER SPINAL CORD INJURY

作　　者：毕昆巍 戚超[1] 高甲科[1] 王湘达[1] 赵夏[1] 于腾波[1] BI Kunwei QI Chao GAO Jiake WANG Xiangda ZHAO Xia YU Tengbo(Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Chin)

机构地区：[1]青岛大学医学院附属医院关节外科,山东青岛266003

出　　处：《青岛大学医学院学报》2016年第6期642-644,共3页Acta Academiae Medicinae Qingdao Universitatis

基　　金：青岛市民生计划项目(13-1-3-26-nsh)

摘　　要：目的研究乙交酯-丙交酯共聚物(PLGA)引导转神经营养素-3(NT-3)基因的小胶质细胞对神经轴突再生的影响,观察神经环路重建后神经功能的恢复情况。方法选取成年雌性Wistar大鼠60只,制备中度脊髓损伤动物模型。建模成功后,将其随机分为空白对照组、PLGA移植组、细胞移植组和联合移植组,每组15只大鼠。并分别向各组大鼠脊髓损伤部位注入生理盐水、PLGA、活化的转NT-3基因小胶质细胞以及活化的转NT-3基因小胶质细胞与PLGA的复合体均5μL。在移植后第1、2、4、6周,根据大鼠恢复情况进行相应运动功能评分(BBB评分)。建模7周后,处死大鼠,每组随机选出5只大鼠取损伤区域脊髓行常规苏木精-伊红染色,光镜下比较损伤脊髓的形态学变化。结果各实验组BBB评分随着时间延长均有所升高,但联合移植组第2、4、6周后肢运动BBB评分较其他各组明显升高(F_(时间)=1 869.848,F_(组别)=1 000.339,F_(时间×组别)=92.161,P<0.01),并且在6周后可见有前后肢体协调活动。镜下观察显示,联合移植组大鼠损伤脊髓的液化坏死区域面积较其他各组小,修复区内可见大量的神经细胞与轴突长入,且分布较均匀,走形更规则。结论 PLGA引导转基因活化小胶质细胞可促进大鼠脊髓损伤后轴突再生和后肢运动功能的恢复。Objective To study the influence of activated transgenic microglia with PLGA on recovery of nerve function after the reconstruction of neural circuits. Methods Sixty female adult Wistar rats were selected for creating an animal model of moderate spinal cord injury （SCI）. After successful modeling, the rats were equally randomized to four groups--blank control group, PLGA transplantation group, cell transplantation group and combined transplantation groups -with 15 rats in each group. An Injection of 5 μL of normal saline, activated NT-3 gene microglia, and PLGA as well as activated NT-3 gene and PLGA complex was respectively injected into the site of SCI of rats in each corresponding group. After the first week, second week, fourth week and sixth week of transplantation, the BBB score was conducted according to the recovery situation of the rats. Seven weeks after the modeling, five rats in each group were randomly selected and scarified, the injured cord tissue was taken for HE staining, and the morphologic variations of the injured cord were compared under light microscope. Results The BBB score of hin＆limb movement in each group increased along with the prolongation of time, but that in the transplantation group was even higher than that in the other groups after second week, fourth week and sixth week （P〈0.01）, and after six weeks, front and rear limb coordination could be seen. Under the microscope, the area of liquefaction necrosis of injured spinal cord in the combined transplantation group was smaller than that in the other groups, in repair area, a large number of nerve cells and axons grew into the area with more uniform distribution and more regular in shape. Conclusion The activated transgenic microglia with PLGA can promote the regeneration of axonal and recovery of the hind-limb motor function in rats with spinal cord injury.

关 键 词：脊髓损伤 小神经胶质细胞 神经生长因子类 转基因 脊髓再生 

分 类 号：R651.2[医药卫生—外科学]