神经激肽（NK1、NK3）对基底核之纹状体神经元兴奋性毒性损伤的不同干预作用

发布时间：2018-10-18 10:55

【摘要】：中枢神经系统(Center Nervous System,CNS)退行性变性疾病的主要病理变化是病变区域神经元的大量死亡。亨廷顿氏病(Huntington disease,HD)是以新纹状体损害为主的锥体外系病,临床表现是不自主的肢体舞蹈样运动,伴有进行性的精神症状及智能衰退。是一种常染色体显性遗传的基底节和大脑皮质变性疾病,病理变化主要位于纹状体、大脑皮质和黑质。新纹状体中以中型中间神经元和纹状体向苍白球或黑质投射的有棘神经元的损害最为严重。以往研究表明在引起HD发生的多种因素中,谷氨酸兴奋性毒性是重要原因之一。但是目前对HD尚无有效的治疗,所以探索阻止谷氨酸兴奋性毒性损伤、保护纹状体神经元变性的新手段,对于完善HD治疗十分必要。神经激肽(Neurokinins)是一个结构相似的速激肽家族,主要包括P物质(Neurokinin-1,NK1)、神经激肽A(NK2)、神经激肽B(NK3),其生物学效应由相应的NK1、NK2和NK3受体(G蛋白偶联受体)来介导。研究表明神经激肽-神经激肽受体在基底核分布十分丰富,它们与基底核神经元之间存在显著的相互作用,PD病人和动物模型的基底核内神经激肽和受体下降。另外,本研究小组以往的研究发现神经激肽受体激动剂对MPTP(1-methyl-4-phenylpyridium-1,2,3,6-tetrahydropyridine,1—甲基—4—苯基—1,2,3,6—四氢吡啶,)诱导PD动物运动症状具有显著影响。提示神经激肽-神经激肽受体参与了基底核生理和病理活动调节过程。Barker和Raffa等提出,神经激肽与神经元变性有关,内源性神经激肽的变化在神经变性疾病发生中可能起着重要作用。那么,神经激肽是否参与纹状体神经元兴奋性毒性损伤的调节过程呢?是需要进一步探讨的问题。该问题的阐明对于揭示神经变性疾病的发生机制及其治疗方法的选择具有重要的理论意义和实际意义。本研究采用海人藻酸(Kainic acid,KA)兴奋性毒损伤模型、分别给予神经激肽NK1、NK3受体的特异性激动剂(senktide、septide)NK3的受体拮抗剂
[Abstract]:The main pathological change of degenerative disease of central nervous system (Center Nervous System,CNS) is the mass death of neurons in the lesion area. Huntington's disease (Huntington disease,HD) is an extrapyramidal disease with neostriatal lesions. It is an autosomal dominant inherited disease of basal ganglia and cerebral cortex. The pathological changes are mainly located in striatum, cerebral cortex and substantia nigra. In the neostriatum, the most serious damage was caused by intermediate neurons and spinous neurons projecting to the globus pallidus or substantia nigra. Previous studies have shown that glutamate excitotoxicity is one of the important causes of HD. However, there is no effective treatment for HD, so it is necessary to explore a new method to prevent glutamate excitotoxic injury and protect striatal neuronal degeneration. Neurokinin (Neurokinins) is a structurally similar family of tachykinins, including substance P (Neurokinin-1,NK1), neurokinin A (NK2) and neurokinin B (NK3), whose biological effects are mediated by the corresponding NK1,NK2 and NK3 receptors (G protein-coupled receptors). The results showed that neurokinin-neurokinin receptors were abundant in the basal nucleus, and there was a significant interaction between them and the neurons in the basal nucleus. The neurokinins and receptors in the basal nucleus of PD patients and animal models were decreased. In addition, our previous studies have found that neurokinin receptor agonists have a significant effect on the motor symptoms of PD induced by MPTP (1-methyl-4-phenylpyridium-36-tetrahydropyridine 1-methyl-4-phenyl-1-trihydropyridine, 1-methyl-4-phenylpyridium-1-tetrahydropyridine, 1-methyl-4-phenylpyridium-1-tetrahydropyridine). It is suggested that neurokinin-neurokinin receptor is involved in the regulation of physiological and pathological activities in the basal nucleus. Barker and Raffa suggest that neurokinin is associated with neuronal degeneration. The changes of endogenous neurokinins may play an important role in the development of neurodegenerative diseases. So is neurokinin involved in the regulation of excitatory injury in striatum neurons? It is a problem that needs to be further explored. The elucidation of this problem is of great theoretical and practical significance in revealing the mechanism of neurodegenerative diseases and the choice of treatment methods. In this study, the excitatory injury model of kainic acid (Kainic acid,KA) was used to give neurokinin NK1,NK3 receptor specific agonist (senktide,septide) NK3 receptor antagonist.
【学位授予单位】：河北师范大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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