本文選題：帕金森病　切入點(diǎn)：左旋多巴誘發(fā)異動癥　出處：《安徽醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景左旋多巴誘發(fā)異動癥(levodopa-induced dyskinesia,LID)是帕金森病藥物治療常見運(yùn)動并發(fā)癥，慢性不規(guī)則多巴胺刺激是LID形成的重要誘因，其發(fā)生與基底節(jié)神經(jīng)元異常同步化和振蕩活動關(guān)系密切�？p隙連接（gap junction，GJ）是由連接相鄰2個(gè)細(xì)胞之間的連接通道排列而成的一種特殊膜結(jié)構(gòu)，參與細(xì)胞間信息、能量和物質(zhì)的交換、代謝偶聯(lián)和電信號偶聯(lián)。GJ是神經(jīng)元同步化活動重要機(jī)制，其功能受到多巴胺能刺激的調(diào)節(jié)。這些線索提示縫隙連接功能異�？赡軈⑴c左旋多巴誘發(fā)異動癥發(fā)生機(jī)制。我們前期的實(shí)驗(yàn)通過免疫組化證實(shí)了LID組紋狀體和運(yùn)動皮層Cx36表達(dá)較PD組和正常對照組顯著增多，支持了該設(shè)想。本實(shí)驗(yàn)將進(jìn)一步探討縫隙連接在左旋多巴誘發(fā)異動癥發(fā)生機(jī)制中的作用。 目的通過了解不同濃度的縫隙連接阻斷劑甘珀酸（carbenoxolon,CBX)及奎寧（quinine,QN）對左旋多巴誘發(fā)異動癥大鼠異動行為的影響，觀察異動癥大鼠縫隙連接蛋白Cx36在不同類型紋狀體神經(jīng)元的表達(dá)差異和基底節(jié)運(yùn)動皮層蛋白水平的變化，探討縫隙連接功能異常在異動癥發(fā)生機(jī)制中的作用。 方法6-羥多巴胺偏側(cè)帕金森病大鼠模型重復(fù)腹腔注射左旋多巴（20mg/kg）和卞絲肼（10mg/kg）共21天，以建立左旋多巴誘發(fā)異動癥模型。將大鼠分為三組：LID組、PD組、正常對照組。①通過LID大鼠腹腔注射不同劑量的CBX與側(cè)腦室注射奎寧來觀察縫隙連接阻斷劑對異動癥大鼠行為學(xué)的影響。②免疫雙標(biāo)法分析各組腦啡肽（ENK）陽性紋狀體傳出神經(jīng)元及小清蛋白（parvalbumin）陽性中間神經(jīng)元CX36表達(dá)情況。③Western-blot檢測各組紋狀體及運(yùn)動皮層Cx36蛋白表達(dá)。 結(jié)果①行為學(xué)研究顯示大劑量(60mg/kg)的甘珀酸腹腔注射和奎寧側(cè)腦室注射（2.5μmol）能減少異動癥大鼠的AIM評分（P0.05）。②免疫雙標(biāo)顯示異動癥大鼠損毀側(cè)紋狀體腦啡肽陽性神經(jīng)元Cx36表達(dá)(57.59%±5.36%)較正常對照組（32.67%±4.22%）和PD組(37.24%±0.86%)增強(qiáng)(F=78.060,P0.01)，小清蛋白陽性中間神經(jīng)元Cx36表達(dá)(68.49%±11.60%)也較正常對照組（40.43%±2.30%）和PD組（31.92%±5.68%）增強(qiáng)（F=39.567,P0.01）。③白質(zhì)印跡檢測顯示異動癥大鼠損毀側(cè)紋狀體和運(yùn)動皮質(zhì)Cx36表達(dá)水平分別為（219.56%±18.12%）、（226.03%±16.33%），高于正常對照組的(104.05%±3.82%)(t=15.389,P＜0.01）、（105.27%±2.82%）(t=8.074,P＜0.01）和PD組的(119.31%±8.92%)(t=13.356,P＜0.01）、（138.20%±17.88%）(t=5.872,P＜0.01）。 結(jié)論左旋多巴誘發(fā)的異動癥大鼠損傷側(cè)紋狀體及運(yùn)動皮層的Cx36蛋白表達(dá)水平增強(qiáng)，紋狀體ENK陽性傳出神經(jīng)元Cx36表達(dá)水平上調(diào)，且Parvalbumin陽性中間神經(jīng)元Cx36表達(dá)水平增高，縫隙連接阻斷劑能有效減少大鼠的異動行為，提示縫隙連接異常可能參與了異動癥的發(fā)生機(jī)制。
[Abstract]:Background levodopa-induced dyskinesia (LIDs) is a common motor complication in the treatment of Parkinson's disease. Chronic irregular dopamine stimulation is an important inducement for the formation of LID. Its occurrence is closely related to abnormal synchronization and oscillatory activity of basal ganglion neurons. Gap junction junction GJ is a special membrane structure arranged by connecting the connecting channels between two adjacent cells and participates in intercellular information. The exchange of energy and matter, metabolic coupling and electrical coupling. GJ are important mechanisms of neuronal synchronization. Its function is regulated by dopaminergic stimulation. These clues suggest that gap junction dysfunction may be involved in the pathogenesis of levodopa-induced dyskinesia. Our previous experiment confirmed the striatum and motility of LID group by immunohistochemistry. Compared with PD group and normal control group, the expression of Cx36 in the arteriocortex was significantly increased. This experiment will further explore the role of gap junction in the pathogenesis of levodopa-induced hyperactivity. Objective to investigate the effects of different concentrations of gap junction blockers carbenoxolonium (CBX) and quinine quinine (QN) on the abnormal behavior induced by levodopa in rats with dyskinesia. To observe the difference of gap junction protein (Cx36) expression in different types of striatum neurons and the changes of basal ganglia motor cortex protein level in rats with dyskinesia, and to explore the role of gap junction dysfunction in the pathogenesis of dyskinesia. Methods the rat model of 6-hydroxydopamine hemiparkinsonism was repeatedly injected intraperitoneally with levodopa (20 mg / kg) and Bensarazide (10 mg / kg) for 21 days in order to establish the model of levodopa induced hyperactivity disorder. The rats were divided into three groups: control group (n = 3) and PD group (n = 10). To observe the effect of gap junction blocker on behavior of rats with dyskinesia by intraperitoneal injection of different doses of CBX and intracerebroventricular injection of quinine in normal control group. 2 Immuno-double standard method for analysis of enkephalin positive striatum in each group. The expression of Cx36 protein in striatum and motor cortex was detected by Western-blot. Results 1Behavioral studies showed that intraperitoneal injection of high-dose carbenic acid (60 mg / kg) and intracerebroventricular injection of quinine (2.5 渭 mol) decreased the AIM score of rats with dyskinesia (P0.050.2-immunoreactive double labeling showed that dyskinetic rats had dyskinesia with dyskinetic rat striatum enkephalin positive neurons. The expression of Cx36 was 57.59% 鹵5.36% and 32.67% 鹵4.22% in control group and 37.24% 鹵0.86 in PD group, respectively.) the expression of Cx36 was increased by 78.060% and 68.49% 鹵11.601% respectively. The expression of Cx36 in striatum was also significantly higher than that in normal control group (40.43% 鹵2.30%) and PD group (31.92% 鹵5.68%). The expression level of Cx36 in the cortex was 219.56% 鹵18.12 鹵226.03% 鹵16.33, which was higher than that in the normal control group (104.05% 鹵3.82% 鹵3.82) and in the PD group (105.27% 鹵2.82% 鹵8.074 P < 0.01) and in PD group (138.20% 鹵17.888.872P < 0.01). Conclusion the expression of Cx36 protein in the injured striatum and motor cortex of rats induced by levodopa-induced dyskinesia is increased, the Cx36 expression of ENK positive efferent neurons in striatum is up-regulated, and the Cx36 expression of Parvalbumin positive intermediate neurons is increased. Gap junction blockers can effectively reduce the abnormal behavior of rats, suggesting that abnormal gap junction may be involved in the pathogenesis of hyperactivity.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R742.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 齊正;金旭;王保國;;依托咪酯對小鼠誘導(dǎo)分化神經(jīng)元縫隙連接子表達(dá)量的影響[J];中國現(xiàn)代神經(jīng)疾病雜志;2010年04期

2 陳寶平,毛紅嬌,夏強(qiáng);庚醇對烏頭堿誘發(fā)大鼠心律失常的影響[J];現(xiàn)代醫(yī)藥衛(wèi)生;2005年14期

，

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