Sertoli细胞促进大鼠胚胎中脑神经前体细胞分化的作用及其对Sertoli细胞DHH基因的相关研究

发布时间：2018-03-05 17:40

本文选题：神经前体细胞　切入点：多巴胺能神经元　出处：《河北医科大学》2005年博士论文　论文类型：学位论文

【摘要】：神经前体细胞(Neural Precursor Cells,NPCs)是一种具有自我更新和多向分化能力的原始细胞,在特定因素影响或诱导下能向神经元和胶质细胞分化。深入研究并获得NPCs对神经系统退行性疾病如帕金森病(Parkinson disease, PD)的细胞移植治疗具有应用前景。已有研究发现,移植经诱导分化的多巴胺(Dopamine, DA)能神经元的PD模型大鼠行为学有显著改善。无论如何,找到稳定的体外诱导方法来保证NPCs能够向DA能神经元分化,即做到人为地操纵细胞分化,是有效地将神经干细胞用于PD临床细胞治疗的关键。尽管已经有诸多此类尝试,但目前尚存在不少问题,包括:①尚未找到成熟的方法来诱导NPCs分化成具有合成特异性递质能力的神经元; ②尚不清楚决定前体细胞分化的确切机制; ③体内实验尚不能证明体外实验已经证实的某些诱导分化因素的作用。为探索从NPCs诱导出DA能神经元的新途径,本研究建立了大鼠睾丸Sertoli细胞与大鼠胚胎中脑NPCs的共培养体系,利用Sertoli细胞分泌的各种活性物质来促进NPCs向DA能神经元分化;在此基础上,本研究又以Sertoli细胞表达的DHH基因为切入点,探讨了Sertoli细胞促进前体细胞分化的可能机制。 Sertoli 细胞是睾丸中特有的体细胞,对发育中的生精细胞提供营养支持和免疫屏障,并能促进精原细胞分化为成熟的精子。Sertoli 细胞具有活跃的分泌功能,能够分泌100 余种不同的蛋白质,其中许多物质与促进DA 能神经元分化的因子相类似。有实验证实,将Sertoli 细胞与其他组织来源的细胞共培养可以影响这些细胞的生长、发育和分化。本研究将Sertoli 细胞和NPCs 共培养后,可以明显增加NPCs 分化为酪氨酸羟化酶(Tyrosine hydroxylase, TH)阳性DA 能神经元的速度和数量。 Desert Hedgehog(DHH)是Hedgehog(HH)分泌型信号分子家族的成员之一,该家族除DHH 外,还包括Sonic Hedgehog(SHH)和Indian Hedgehog(IHH)基因,它们分别编码Shh、Ihh 和Dhh 蛋白。DHH 分布
[Abstract]:Neural Precursor cells (NPCs) are a kind of primordial cells with the ability of self-renewal and multi-differentiation. It can differentiate into neurons and glial cells under the influence or induction of specific factors. Further study and acquisition of NPCs for the treatment of neurodegenerative diseases such as Parkinson disease (PDD) has a promising prospect. The behavior of PD model rats transplanted with differentiated dopaminergic neurons was significantly improved. In any case, a stable in vitro induction method was found to ensure that NPCs could differentiate into DA neurons, that is, to manipulate the differentiation of cells artificially. Is the key to the effective use of neural stem cells in the treatment of PD clinical cells. Although there have been many such attempts, there are still many problems. Including: 1 has not yet found a mature way to induce NPCs to differentiate into neurons with the ability to synthesize specific transmitters; 2 it is not yet clear to determine the exact mechanism of precursor cell differentiation; 3 in vivo experiments have not been able to prove that the in vitro experiment. The role of certain factors in inducing differentiation was confirmed. In order to explore a new way to induce DA neurons from NPCs, a co-culture system between rat testicular Sertoli cells and rat embryonic midbrain NPCs was established, and various active substances secreted by Sertoli cells were used to promote the differentiation of NPCs into DA neurons. On this basis, the possible mechanism of Sertoli cells promoting the differentiation of precursor cells was explored by using the DHH gene expressed in Sertoli cells as the breakthrough point. Sertoli cells are specific somatic cells in the testis, which provide nutritional support and immune barrier for developing spermatogenic cells, and promote the differentiation of spermatogonia into mature spermatozoa. Sertoli cells have active secretory function. It can secrete more than 100 different proteins, many of which are similar to the factors that promote the differentiation of DA neurons. Experiments have shown that co-culture of Sertoli cells with cells from other tissues can affect the growth of these cells. In this study, Sertoli cells co-cultured with NPCs could significantly increase the rate and number of NPCs differentiating into tyrosine hydroxylase (TH3) -positive DA neurons. Desert Hedgehog (Desert) is a member of the secretory signal molecule family of Hedgehog (HH). In addition to DHH, the family also includes Sonic Hedgehog) and Indian Hedgehog (IHH) genes, which encode Shhhh and Dhh protein .DHH distribution, respectively.
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R329

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