BDNF基因工程细胞对帕金森大鼠纹状体多巴胺及其代谢物影响的研究  

Study on the levels of DA and metabolite in striatum in rats with Parkinson’s disease treated by BDNF gene modified bone mesenchymal stem cells

作　　者：赵钢勇[1] 崔蕾[2] 高娟[2] 代瑞廷[2] 张平[2] 

机构地区：[1]河北大学生物技术研究中心 [2]河北大学附属医院神经内科,保定071000

出　　处：《中国应用生理学杂志》2013年第1期82-85,I0004,共5页Chinese Journal of Applied Physiology

基　　金：河北省科学技术研究与发展计划项目(08206120D)

摘　　要：目的:观察经侧脑室移植pIRESneo-EGFP-BDNF修饰骨髓间充质干细胞(MSCs)对帕金森病(PD)大鼠纹状体多巴胺(DA)及代谢产物的影响。方法:采用电穿孔法将pIRESneo-EGFP-BDNF转染至骨髓MSCs;制备PD大鼠模型,随机分为Sham组,PD组,MSCs组,脑源性神经生长因子(BDNF)组,经侧脑室移植MSCs或pIRESneo-EGFP-BDNF修饰骨髓MSCs,术后2周,4周,8周,腹腔注射阿朴吗啡(APO)诱导PD大鼠旋转行为;应用高效液相色谱测定各组大鼠纹状体内多巴胺(DA)、高香草酸(HVA)及二羟苯乙酸(DOPAC)。结果:移植术后2周,4周,8周BDNF组、MSCs组大鼠与PD组比较旋转次数明显减少(P<0.05),以BDNF组改善更为明显。移植细胞干预PD模型8周后BDNF组、MSCs组大鼠纹状体DA、HVA、DOPAC较PD组明显提高(P<0.01),以BDNF组更为显著。结论:经侧脑室移植pIRESneo-EGFP-BDNF修饰的骨髓MSCs干预PD大鼠模型,显著降低PD大鼠纹状体内DA代谢率,提高DA水平,改善PD大鼠的行为能力。Objective： To investigate the effects of dopamine（DA） and metabolite in striatum of Parkinson’s disease（PD） rats treated by bone mesenchymal stem cells（MSCs） modified by plasmid pIRESneo-EGFP-BDNF.Method： pIRESneo-EGFP-BDNF was transfected to MSCs with electroproation.The rat models of PD were set up by 6-OHDA and then divided into four groups randomly,which were Sham group,PD group,BDNF group.The rotating behavior of rat models induced by apomorphine（APO） intraperitoneally which transplanting bone MSCs or MSCs modified by plasmid pIRESneo-EGFP-BDNF through cerebral lateral ventricle after 2,4 and 8 weeks.The levels of DA,homovanillic acid（HVA）,dihydroxy-phenylacetic acid（DOPAC） were measured by high performance liquid chromatography（HPLC） in striatum of each group.Results： The rotation numbers（r/min） of MSCs group or BDNF group in the 2nd,4th and 8th week after transplanting were significantly decreased compared with that of PD group（P0.05）.Those of BDNF group were exespecially significant compared with those of MSCs group（P0.05）.The levels of DA,HVA,DOPAC and the ratios of DA/HVA,DA/DOPAC in stratum after PD rats intervented by transplating cells through cerebral lateral ventricle after eight weeks were increased significantly in BDNF group or MSCs group while compared with PD group,especially in BDNF group.Conclusion： The behavior of rat with PD was improved significantly by increasing the levels of DA and decreasing metabolic rate of DA in striatum while transplanting BDNF modified bone MSCs through cerebral lateral ventricle.

关 键 词：脑源性神经生长因子 间充质干细胞 质粒 多巴胺 高香草酸 二羟苯乙酸 帕金森病 

分 类 号：R741[医药卫生—神经病学与精神病学]