發(fā)布時間：2018-10-18 10:55

【摘要】：中樞神經系統(Center Nervous System,CNS)退行性變性疾病的主要病理變化是病變區(qū)域神經元的大量死亡。亨廷頓氏病(Huntington disease,HD)是以新紋狀體損害為主的錐體外系病,臨床表現是不自主的肢體舞蹈樣運動,伴有進行性的精神癥狀及智能衰退。是一種常染色體顯性遺傳的基底節(jié)和大腦皮質變性疾病,病理變化主要位于紋狀體、大腦皮質和黑質。新紋狀體中以中型中間神經元和紋狀體向蒼白球或黑質投射的有棘神經元的損害最為嚴重。以往研究表明在引起HD發(fā)生的多種因素中,谷氨酸興奮性毒性是重要原因之一。但是目前對HD尚無有效的治療,所以探索阻止谷氨酸興奮性毒性損傷、保護紋狀體神經元變性的新手段,對于完善HD治療十分必要。 神經激肽(Neurokinins)是一個結構相似的速激肽家族,主要包括P物質(Neurokinin-1,NK1)、神經激肽A(NK2)、神經激肽B(NK3),其生物學效應由相應的NK1、NK2和NK3受體(G蛋白偶聯受體)來介導。研究表明神經激肽-神經激肽受體在基底核分布十分豐富,它們與基底核神經元之間存在顯著的相互作用,PD病人和動物模型的基底核內神經激肽和受體下降。另外,本研究小組以往的研究發(fā)現神經激肽受體激動劑對MPTP(1-methyl-4-phenylpyridium-1,2,3,6-tetrahydropyridine,1—甲基—4—苯基—1,2,3,6—四氫吡啶,)誘導PD動物運動癥狀具有顯著影響。提示神經激肽-神經激肽受體參與了基底核生理和病理活動調節(jié)過程。Barker和Raffa等提出,神經激肽與神經元變性有關,內源性神經激肽的變化在神經變性疾病發(fā)生中可能起著重要作用。那么,神經激肽是否參與紋狀體神經元興奮性毒性損傷的調節(jié)過程呢?是需要進一步探討的問題。該問題的闡明對于揭示神經變性疾病的發(fā)生機制及其治療方法的選擇具有重要的理論意義和實際意義。 本研究采用海人藻酸(Kainic acid,KA)興奮性毒損傷模型、分別給予神經激肽NK1、NK3受體的特異性激動劑(senktide、septide)NK3的受體拮抗劑
[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.
【學位授予單位】：河北師范大學
【學位級別】：碩士
【學位授予年份】：2006
【分類號】：R363

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相關期刊論文 前1條

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本文編號：2278906