移植骨髓间充质干细胞对大鼠脑梗死后神经元凋亡的影响  

Effect of Transplantation of Bone Marrow-derived Mesenchymal Stem Cells on the Apoptosis of Neurons in Ischemic Rats

作　　者：包新杰[1] 魏俊吉[1] 冯铭[1] 卢珊[2] 赵春华[2] 王任直[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院神经外科,北京100730 [2]中国医学科学院北京协和医学院基础医学研究所组织工程中心,北京100730

出　　处：《协和医学杂志》2011年第1期19-23,共5页Medical Journal of Peking Union Medical College Hospital

基　　金：国家863计划重点项目(2006AA02A115)

摘　　要：目的探讨移植骨髓间充质干细胞(bone marrow-derived mesenchymal stemcells,BMSCs)治疗大鼠脑梗死及其减轻半暗带神经元的凋亡作用。方法采集成人志愿者骨髓,分离培养BMSCs;线栓法建立大鼠大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)2h再灌注脑梗死模型;建模后第3天分别立体定向脑内移植5×105BMSCs和等量生理盐水,改良神经功能损害评分(modified neurological severity scores,mNSS)观察神经功能恢复;建模后第14天TUNEL法检测梗死周边神经细胞凋亡;建模后第28天免疫荧光染色检测梗死周边神经元的存活;采用依红-苏木素染色评估梗死体积。结果治疗组和对照组比较,梗死周边TUNEL阳性细胞显著减少(P=0.017),而神经元核抗原(neuronal nuclei antigen,NeuN)阳性细胞显著增多(P=0.015);同时,BMSCs可显著降低MCAO大鼠的相对梗死体积(P=0.041);mNSS评分显示,从MCAO后第14天开始,治疗组评分均显著低于对照组(P<0.05)。结论脑梗死急性期移植BMSCs可显著减少半暗带神经元凋亡,缩小梗死范围,有效促进神经功能的恢复。Objective To investigate the apoptosis of neurons in the penumbra of cerebral ischemic rats transplanted with bone marrow derived-mesenchymal stem cells（BMSCs）.Methods Bone marrow of a healthy adult volunteer was collected,and BMSCs were cultivated and harvested.Adult rats subjected to 2 h middle cerebral artery occlusion（MCAO）were randomly assigned to the BMSCs-treated group（n=12）and the control group（n=12）,in which rats were transplanted with 5×105 BMSCs or saline,respectively,into the ipsilateral brain parenchyma on the 3rd post-MCAO day.The modified neurological severity scores（mNSS）was used to measure functional recovery.On the 14th post-MCAO day,apoptotic cells in the penumbra were detected by TUNEL analysis.On the 28th post-MCAO day,neurons were stained by immunoflu-orescence,and hematoxylin-eosin staining was used to evaluate the relative ischemic volume.Results TUNEL-positive cells were significantly reduced（P=0.017）,and in contrast,neuronal nuclei antigen（NeuN）-positive cells were significantly increased（P=0.015）in the penumbra in BMSCs-treated group compared with control group.The relative ischemic volume was decreased in the BMSCs-treated group（28.3±4.5）% compared with the control group（36.8±5.6）%（P=0.041）.The mNSS was significantly decreased in BMSCs-treated group at each time point starting on the 14th post-MCAO day compared with control group（P〈0.05）.Conclusion BMSCs treatment can decrease ischemic volume and improve functional recovery after cerebral ischemia,which may,at least partially,attribute to the reduced apoptosis of neurons in the penumbra.

关 键 词：脑梗死 间充质干细胞 神经元 凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学] R34[医药卫生—临床医学]