氯化锂对脊髓损伤大鼠内源性神经干细胞的影响  

Effects of lithium chloride on endogenous neural stem cells in rats after spinal cord injury

作　　者：徐启飞[1] 周初松[1] 靳安民[1] 兰小勇[1] 吕志德[1] 

机构地区：[1]南方医科大学珠江医院骨科中心,广东省广州市510282

出　　处：《中国组织工程研究与临床康复》2009年第19期3645-3650,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:对于脊髓损伤的治疗,移植外源性神经干细胞仍面临着诸多难题,因此激活内源性神经干细胞的"补充治疗"策略成为近来研究热点。已发现氯化锂可以明显抑制神经干细胞的分化而促进其增殖,其效应与Wnt信号通路有关。目的:探讨氯化锂对大鼠脊髓损伤后内源性神经干细胞的影响。设计、时间及地点:随机对照动物实验,于2008-03/08在珠江医院中心实验室进行。材料:Wistar成年雌性大鼠55只,分为3组:正常对照组5只、单纯损伤组25只、氯化锂治疗组25只。氯化锂为广州光华化学试剂厂产品。方法:单纯损伤组、氯化锂治疗组大鼠采用经典Allens重物坠落法在T10段制作急性脊髓损伤模型。从造模后1h开始,氯化锂治疗组经腹腔注射氯化锂3mmol/(kg·d),直至取材;单纯损伤组同法给予等量生理盐水;正常对照组不作任何处理。各组取材前24h腹腔注射Brdu溶液进行标记,每8h注射1次,共3次。对距离损伤中心5mm处的脊髓进行Brdu、连环蛋白免疫组化检测。主要观察指标:BrdU阳性细胞数及连环蛋白阳性表达面积。结果:正常对照组脊髓中央管周围及外膜可见少量Brdu阳性细胞,几乎无连环蛋白阳性表达。单纯损伤组造模后24h即可见大量Brdu阳性细胞及微量连环蛋白表达,1周时两者达到高峰,主要分布于损伤脊髓周围的灰质和室管膜区,2周后开始明显减少,4周时仅见少量Brdu阳性细胞及连环蛋白阳性表达。与单纯损伤组比较,造模后24h氯化锂治疗组Brdu阳性细胞及连环蛋白的表达无显著性差异,1周时在中央管周围、外膜、灰质中Brdu阳性细胞数及连环蛋白表达量明显增多(P<0.05),至2周时仍处于较高水平,4周时仍有大量Brdu阳性细胞及连环蛋白表达。结论:脊髓损伤后氯化锂的应用可以明显提高损伤脊髓组织内连环蛋白的表达,伴随着连环蛋白浓度的提高及持续表达,促进内源性神经干细�BACKGROUND： For treatment of spinal cord injury, exogenous neural stem cell transplantation still faces many problems. Thus, the strategy of supplementary treatment of activating exogenous neural stem cells has been a hot focus. It has been found that lithium chloride can significantly inhibit differentiation and promote proliferation of neural stem cells, whose effects are correlated to Wnt signal pathway. OBJECTIVE： To investigate the effect of lithium on endogenous neural stem cells after spinal cord injury in rats. DESIGN, TIME AND SETTING： The randomized controlled animal study was performed at the Central Laboratory, Zhujiang Hospital from March to August 2008. MATERIALS： A total of 55 adult female Wistar rats were assigned into normal control group （n=5）, simple injury group （n=25）, and lithium chloride group （n=25）. Lithium chloride was purchased from Guanghua, Guangzhou, China. METHODS： In the simple injury group and lithium chloride group, rat models of acute spinal cord injury at T10 segment were made by Aliens method. From 1 hour following model induction, rats in the lithium chloride group received 3 mmol/kg per day lithium chloride through intraperithoneal injection. Samples were directly obtained. In the simple injury group, rats received an equal volume of saline. Rats in the normal control group were left intact. 24 hours before samples were obtained, rats in each group were intraperitoneally injected with Brdu solution for labeling, once every 8 hours, totally 3 times. Spinal cord at 5 mm from the center of damage region received Brdu, catenin immunohistochemistry. MAIN OUTCOME MEASURES： BrdU-positive cell number and area of catenin-positive expression were measured. RESULTS： There were a few Brdu-positive cells and less expression of catenin in the center canal and adventitia of spinal cord in the normal control group. Many Brdu-positive cells and a little expression of catenin were found in gray matter and ependyma of injury area in the simple injury group 24 hours af

关 键 词：内源性神经干细胞 氯化锂 脊髓损伤 糖原合成激酶 

分 类 号：R394.2[医药卫生—医学遗传学]