骨髓基质细胞条件培养液诱导神经干细胞分化的信号转导机制  

The Signal Transduction Pathway of NSCs' Differentiation Induced by BMSCs Conditioned Medium

作　　者：马芹颖[1,2] 温雅[2] 顾平[1,2] 王彦永[1,2] 王铭维[1,2] 崔冬生[2] 刘力[2] 

机构地区：[1]河北医科大学第一医院神经内科,石家庄050031 [2]河北省脑老化与认知神经科学实验室,石家庄050031

出　　处：《细胞生物学杂志》2009年第3期424-428,共5页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(No.30400138);河北省自然科学基金(No.2008000993)资助项目~~

摘　　要：研究MAPK信号转导通路在骨髓基质细胞条件培养液诱导神经干细胞分化中的作用及机制。用骨髓基质细胞条件培养液培养神经干细胞,并在培养体系中加入MAPK信号转导通路抑制剂PD98059(ERK1/2通路抑制剂)、SB203580(p38通路抑制剂)和genistin(JNK通路抑制剂),7天后经免疫荧光染色鉴定其后代中神经元和星形胶质细胞的比例,并将骨髓基质细胞条件培养液进行蛋白质微阵列检测。结果发现与对照组相比,PD98059和SB203580组神经干细胞分化为神经元比例降低,而星形胶质细胞比例增高,蛋白质微阵列测检发现骨髓基质细胞条件培养液中含有IL-4、IL-6、LIX和TNF-α4种细胞因子。研究结果显示骨髓基质细胞分泌的IL-4、IL-6、LIX和TNF-α4种细胞因子可能通过ERK1/2和p38信号转导通路调节神经干细胞的分化。To explore the effect and mechanism of mitogen-activated protein kinase （MAPK） on the procedure that bone marrow stromal cells （BMSCs） conditioned medium regulate the differentiation of neural stem cells （NSCs）. BMSCs conditioned medium was used to culture NSCs, MAPKs signal transduction pathway inhibitor, PD98059 （an inhibitor of ERK1/2 signal transduction pathway）, SB203580 （an inhibitor of p38 signal transduction pathway） and genistin （an inhibitor of JNK signal transduction pathway） was added in the conditioned medium, respectively. Immunocytochemistry was performed to identify the neurons and astrocytes in the offspings at the 7th day and the percentage of each type further as worked out, then BMSCs conditioned medium was detected by protein microarray for a further study for the mechanism. The percentage of neurons in the PD98059 group and SB203580 group was significantly decreased, but the percentage of astrocytes was significantly increased compared with the control group. Four cytokines including IL-4, IL-6, LIX and TNF-α were detected in the BMSCs conditioned medium. The dissolvable molecules of IL-4, IL-6, LIX and TNF-α secreted by BMSCs could regulate the differentiation of NSCs probably via the ERK1/2 and p38 signal transduction pathway.

关 键 词：MAPK信号转导通路 神经干细胞 骨髓基质细胞 细胞因子 蛋白质微阵列分析 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]