人胚DA能神经元移植于帕金森氏病猴模型的TH免疫细胞化学的研究  

FATE OF HUMAN FETAL DOPAMINE NEURONS TRANSPLANTED INTO RHESUS MONKEY MODEL OF PARKINSON'S DISEASE:A TYROSINE HYDROXYLASE IMMUNOCYTOCHEMICAL STUDY

作　　者：蒋芝华[1] 刘振国[1] 陈生弟[1] 周文波[1] 蔡军[1] 倪紫美[1] 周长福[1] 

机构地区：[1]中国科学院上海生理研究所,上海第二医科大学附属瑞金医院神经内科

出　　处：《生理学报》1995年第1期31-37,共7页Acta Physiologica Sinica

基　　金：国家自然科学基金;国家科委中国科学院匹配经费资助

摘　　要：为了对人胚黑质ＤＡ神经元移植治疗ＰＤ人的临床应用作出客观评估，将８—１２周人胚黑质细胞移植到用ＭＰＴＰ诱发的偏侧ＰＤ猴新纹状体内。实验动物分别存活２个月、５个月和１年后，用ＴＨ免疫细胞化学方法对被移植的人胚ＤＡ细胞的存活和与宿主间的突触联系进行检查。在光镜下可见被移植侧的新纹状体内有ＴＨ阳性细胞，它们成小群散在分布，每小群有３—１０个细胞。ＴＨ阳性细胞的轴突延伸到整个新纹状体，树突呈现出正常发育过程中特有的念珠状结节形态变化。在电镜下观察到ＴＨ阳性轴突终末与宿主新纹状体内的ＴＨ阴性树突干和树突棘形成对称型或不对称型突触，ＴＨ阳性轴突终末与ＴＨ阴性轴突终末形成对称型突触，ＴＨ阴性轴突终末与ＴＨ阳性胞体和树突形成突触。上述突触在移植后５个月的比２个月的多，移植后１年的最多。这结果表明８—１２周人胚ＤＡ能神经元移植到ＰＤ猴新纹状体能存活和发育并与宿主建立突触联系，甚至在移植后２个月这种联系已开始形成。猴与人在种系发生上相近，属灵长类。因此可推测，早期人胚ＤＡ能神经元移植到ＰＤ人新纹状体后，可能具有类似的形态学发育特性。To predicate the value of human fetal substantia nigra transplantation in clinical treatment of Parkinson's disease (PD), dissociated cells of substantia nigra from 8-12week old abortive human fetus were grafted into the neostriatum of 5 adult rhesus monkeys with hemiparkinsonism induced by unilateral injection of MPTP. At 2, 5 and 12months after transplanting the monkeys were sacrificed for tyrosine hydroxylase (TH)immunocytochemistry to examine the survival and possible synaptic contact of transplanted dopamine (DA) neurons. Transplanted TH immunoreactive cells took a patternof patches scattered in the neostriatum. Each of the cell patches consisted of 3 -1 0 cells. The TH immunoreactive fiber network was seen in the neostriatum. Electron microscopic survey revealed that TH+ buttons arising from grafted DA neurons formedsymmetric or asymmetric synapses with TH- dendritic shafts/spines, and TH + dendrites were seen to form synapses with TH- axons of the host. Additionally, there werea few synapses formed by TH+ axconal terminals with negative buttons. The results suggest that DA neurons from 8-12 week old abortive human fetus are able to survivegrafting into the neostriatum of monkey, a species phylogenetically very close to human, and to establish reciprocal synaptic connectivity with the host even at 2 monthspost-transplanting. It is, therefore, inferable that embryonic human DA neurons transplanted into human neostriatum may have the same fate as in monkeys.

关 键 词：震颤性麻痹 多巴胺神经元 移植术 黑质 新纹状体 

分 类 号：R651.11[医药卫生—外科学] R742.505[医药卫生—临床医学]