TH基因转染的骨髓源性神经干细胞在不同移植途径下对PD大鼠模型治疗作用的实验研究
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摘要
一、概述
帕金森病(Parkinson's Disease PD)是一种以锥体外系黑质多巴胺能神经元进行性损害为主要病理表现的中枢神经系统退变性疾病。其病因及发病机制尚不能够确定，而且目前的内、外科治疗只限于对患者症状的控制，不能阻止其病程的进展。近年来，随着神经干细胞研究的深入以及基因工程技术的日臻完善，使神经干细胞的基因方法治疗帕金森病成为可能。
目前已经明确，人脑内多巴胺(dopamine DA)含量约90％左右集中于中脑，尤其是黑质-纹状体区，当此处DA含量下降超过70％时，患者将开始出现PD的临床表现，而DA在脑内生成代谢过程中，中脑内酪氨酸羟化酶(tyrosinehydroxylase TH)起到关键作用，是DA生成的限速酶。研究显示：PD患者脑内TH及THmRNA的含量是同步降低的，而补充中脑TH，可以提高脑内DA含量，并可以改善PD症状。因此，在PD基因治疗中TH基因自然成为治疗基因的首选。
Parkinson's disease (PD) is a neurodegenerative disorder in the central nerve system which characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The etiopathogenisis and mechanism of PD is not known. And the current medicinal and surgical treatments are significantly limited within controlling the parts of symptoms, and could not be able to prevent the neurodegenerative progress of PD. With the developed technique of the genetic engineering and the developing research of nerve stem cells (NSCs), it is be possible for NSCs modified with medicative gene to treat PD, which become a cheerful prospect.
Up to now, it was identified that there are about of 90% dopamine (DA) localized in midbrain, especially in nigra-striatum. The symptoms of PD will occur when the content of DA in this area decreases more than 70%. And tyrosine hydroxylase (TH) is the rate-limiting enzyme of producing dopamine (DA) for the dopaminergic neurons. Some research shows that the content of TH is depressed synchronously with THmRNA, and the content of DA will be enhanced and the symptom improved, if TH in the middle-brain is supplied. Therefore TH gene is the first choice of medicative genes to treat PD.
Stem cells are a kind of cells mass with abilities of massive self-replication in vivo or in vitro and persistent dissymmetric cells divission, which include embryonic stem cells, adult stem cells and stem cells derived from marrow, et al. Since all kinds of stem cells are widely accredited and able to take therapic effect on PD models in the experiments, especially the research on bone morrow stem cells (BMSCs) is a hot spot, while the other two
帕金森病(Parkinson's Disease PD)是一种以锥体外系黑质多巴胺能神经元进行性损害为主要病理表现的中枢神经系统退变性疾病。其病因及发病机制尚不能够确定，而且目前的内、外科治疗只限于对患者症状的控制，不能阻止其病程的进展。近年来，随着神经干细胞研究的深入以及基因工程技术的日臻完善，使神经干细胞的基因方法治疗帕金森病成为可能。
目前已经明确，人脑内多巴胺(dopamine DA)含量约90％左右集中于中脑，尤其是黑质-纹状体区，当此处DA含量下降超过70％时，患者将开始出现PD的临床表现，而DA在脑内生成代谢过程中，中脑内酪氨酸羟化酶(tyrosinehydroxylase TH)起到关键作用，是DA生成的限速酶。研究显示：PD患者脑内TH及THmRNA的含量是同步降低的，而补充中脑TH，可以提高脑内DA含量，并可以改善PD症状。因此，在PD基因治疗中TH基因自然成为治疗基因的首选。
Parkinson's disease (PD) is a neurodegenerative disorder in the central nerve system which characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The etiopathogenisis and mechanism of PD is not known. And the current medicinal and surgical treatments are significantly limited within controlling the parts of symptoms, and could not be able to prevent the neurodegenerative progress of PD. With the developed technique of the genetic engineering and the developing research of nerve stem cells (NSCs), it is be possible for NSCs modified with medicative gene to treat PD, which become a cheerful prospect.
Up to now, it was identified that there are about of 90% dopamine (DA) localized in midbrain, especially in nigra-striatum. The symptoms of PD will occur when the content of DA in this area decreases more than 70%. And tyrosine hydroxylase (TH) is the rate-limiting enzyme of producing dopamine (DA) for the dopaminergic neurons. Some research shows that the content of TH is depressed synchronously with THmRNA, and the content of DA will be enhanced and the symptom improved, if TH in the middle-brain is supplied. Therefore TH gene is the first choice of medicative genes to treat PD.
Stem cells are a kind of cells mass with abilities of massive self-replication in vivo or in vitro and persistent dissymmetric cells divission, which include embryonic stem cells, adult stem cells and stem cells derived from marrow, et al. Since all kinds of stem cells are widely accredited and able to take therapic effect on PD models in the experiments, especially the research on bone morrow stem cells (BMSCs) is a hot spot, while the other two
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