發(fā)布時間：2018-04-20 18:14

  本文選題：蒼白球 + 神經(jīng)降壓素　； 參考：《青島大學(xué)》2007年碩士論文

【摘要】： 蒼白球(globus pallidus，GP)是基底神經(jīng)節(jié)間接環(huán)路的重要核團，在機體運動功能調(diào)節(jié)中起著重要的作用。神經(jīng)降壓素(neurotensin，NT)是由13個氨基酸組成的肽類物質(zhì)。在中樞神經(jīng)系統(tǒng)，神經(jīng)降壓素作為神經(jīng)遞質(zhì)或神經(jīng)調(diào)質(zhì)發(fā)揮重要作用，并且與中樞神經(jīng)系統(tǒng)疾病密切相關(guān)。在6-OHDA損毀的大鼠，全身給予一種可以穿過血腦屏障的神經(jīng)降壓素類似物，可以產(chǎn)生抗帕金森病效應(yīng)。形態(tài)學(xué)研究證實，蒼白球接受來自紋狀體的神經(jīng)降壓素能纖維支配，并且表達有神經(jīng)降壓素1型和2型受體。目的：觀察神經(jīng)降壓素對正常大鼠和帕金森病模型大鼠蒼白球神經(jīng)元放電頻率的影響，以及神經(jīng)降壓素對清醒大鼠整體姿勢行為的調(diào)節(jié)。方法：本實驗采用三管微電極細胞外電生理記錄以及清醒狀態(tài)下核團給藥等實驗方法。結(jié)果：1．在正常大鼠蒼白球記錄到的49個神經(jīng)元中，壓力注射0.1mM神經(jīng)降壓素可以興奮其中的24個神經(jīng)元，加藥前放電頻率為10.28±1.48Hz，加藥后放電頻率為14.86±2.01Hz(P＜0.001)，放電頻率平均增加47.41±4.43％。在濃度從0.001mM到1mM范圍內(nèi)，神經(jīng)降壓素對蒼白球神經(jīng)元放電頻率的增加呈鐘型的量效依賴關(guān)系。利用192IgG-saporin破壞蒼白球膽堿能神經(jīng)元后，在記錄到的24個蒼白球神經(jīng)元中，0.1 mM神經(jīng)降壓素可以興奮其中的9個神經(jīng)元，放電頻率平均增加36.67±7.29％，與正常對照組相比沒有明顯差異(P＞0.05)。2．神經(jīng)降壓素羧基末端片段，神經(jīng)降壓素(8-13)，可以產(chǎn)生與神經(jīng)降壓素相似的興奮效應(yīng)，3mM神經(jīng)降壓素(8-13)可使蒼白球神經(jīng)元放電頻率平均增加60.3±8.96％(P＜0.001)。但是其氨基末端片段，神經(jīng)降壓素(1-8)，對蒼白球神經(jīng)元放電頻率沒有任何影響。3．蒼白球神經(jīng)元給予非選擇性神經(jīng)降壓素受體拮抗劑SR142948A，或者選擇性神經(jīng)降壓素1型受體拮抗劑SR48692，均可阻斷神經(jīng)降壓素所致的興奮效應(yīng)。4．在6-OHDA帕金森病模型大鼠損毀側(cè)蒼白球記錄到的20個神經(jīng)元中，0.1 mM神經(jīng)降壓素可以興奮其中的8個神經(jīng)元，其放電頻率平均增加38.09±5.32％。而在帕金森病模型大鼠損毀對側(cè)蒼白球記錄到的17個神經(jīng)元中，，0.1mM神經(jīng)降壓素可以興奮其中的10個神經(jīng)元，放電頻率平均增加85.88±18.91％，較損毀側(cè)的興奮效應(yīng)明顯增加(P＜0.05)。5．進一步實驗觀察了蒼白球神經(jīng)降壓素對大鼠姿勢行為的影響。在腹腔注射氟哌啶醇的條件下，大鼠單側(cè)蒼白球微量注射神經(jīng)降壓素(0.1mM)可以引起明顯的對側(cè)肢體偏轉(zhuǎn)行為，這種行為可以被SR48692所阻斷。結(jié)論：電生理學(xué)和行為學(xué)研究結(jié)果揭示神經(jīng)降壓素通過激活神經(jīng)降壓素1型受體興奮蒼白球神經(jīng)元。該結(jié)果為進一步探討蒼白球神經(jīng)降壓素在機體運動障礙性疾病發(fā)病中的作用提供了理論和實驗依據(jù)。
[Abstract]:Globus pallidusus GP) is an important nucleus in the indirect loop of basal ganglia and plays an important role in the regulation of motor function. Neurotensin NT is a peptide of 13 amino acids. Neurotensin plays an important role as a neurotransmitter or neuromodulator in the central nervous system and is closely related to central nervous system diseases. In 6-OHDA damaged rats, systemic administration of a neurotensin analogue that crosses the blood-brain barrier produces an anti-Parkinson 's disease effect. Morphological studies showed that the globus pallidus was innervated by neurotensin fibers from the striatum and expressed neurotensin type 1 and type 2 receptors. Aim: to observe the effects of neurotensin on the discharge frequency of neurons in the globus pallidus of normal and Parkinson's disease rats and the regulation of neurotensin on the global postural behavior of conscious rats. Methods: three-tube microelectrode cells were used to record the external electrophysiology and to receive the drug in the conscious state. The result is 1: 1. Among the 49 neurons recorded in the globus pallidus of normal rats, 24 neurons were excited by pressure injection of 0.1mM neurotensin. The discharge frequency was 10.28 鹵1.48 Hz before administration, and 14.86 鹵2.01Hz(P < 0.001g after injection. The discharge frequency increased 47.41 鹵4.43 on average. In the range of concentration from 0.001mM to 1mM, the increase of neurotensin on the discharge frequency of globus pallidus neurons was in a dose-dependent manner. After 192IgG-saporin was used to destroy the cholinergic neurons of the globus pallidus, 9 of the 24 neurons of the globus pallidus were excited by 0.1 mm neurotensin, and the discharge frequency increased by 36.67 鹵7.29 on average. There was no significant difference compared with the normal control group (P > 0.05). The end segment of carboxyl group of neurotensin, neurotensin 8-13, which can produce an excitatory effect similar to that of neurotensin, can increase the discharge frequency of neurons in the globus pallidus by an average of 60.3 鹵8.96 (P < 0.001). But its amino terminal segment, neurotensin 1-8, had no effect on the discharge frequency of neurons in the globus pallidus. The excitatory effect of neurotensin induced by neurotensin was blocked by either the non-selective neurotensin receptor antagonist SR142948A or the selective neurotensin 1 receptor antagonist SR48692. Among the 20 neurons recorded in the damaged globus pallidus of 6-OHDA Parkinson's disease model, 0. 1 mm neurotensin could excite 8 of them, and its discharge frequency increased by 38. 09 鹵5. 32 on average. However, in the 17 neurons recorded in the contralateral globus pallidus of Parkinson's disease model, 0.1 mm neurotensin could excite 10 of the neurons, and the discharge frequency was increased by 85.88 鹵18.91 on average, which was significantly higher than that in the damaged side (P < 0.05). The effects of globus pallidus neurotensin on postural behavior in rats were further investigated. Under the condition of intraperitoneal injection of haloperidol, microinjection of neurotensin (0.1 mm) into the unilateral globus pallidus could induce obvious contralateral limb deflection, which could be blocked by SR48692. Conclusion: the results of electrophysiological and behavioral studies indicate that neurotensin excites globus pallidus neurons by activating neurotensin 1 receptor. The results provide a theoretical and experimental basis for the further study of the role of globus pallidus neurotensin in the pathogenesis of dyskinesia.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R33

【共引文獻】

相關(guān)碩士學(xué)位論文 前1條

1 剛書成;神經(jīng)降壓肽在脊髓前角的分布及其在神經(jīng)病理痛中的作用研究[D];華中科技大學(xué);2006年

本文編號：1778865