本文關(guān)鍵詞： 帕金森病 左旋多巴 異動(dòng)癥 局部場(chǎng)電位　出處：《南方醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：研究目的:左旋多巴誘導(dǎo)異動(dòng)癥(Levodopa induced dyskinesia,LID)是晚期帕金森病(Parkinson disease,PD)患者常見的致殘性服藥并發(fā)癥,異動(dòng)癥發(fā)病機(jī)制目前尚未闡明。局部場(chǎng)電位記錄(Local field potential,LFP)是研究PD及其運(yùn)動(dòng)并發(fā)癥LID的電生理機(jī)制重要手段。目前尚缺乏利用局部場(chǎng)電位技術(shù),記錄LID大鼠基底節(jié)背外側(cè)紋狀體(dorsolateral striatum,dStr)和黑質(zhì)網(wǎng)狀部(substantia nigra pars reticulate,SNr)的振蕩電活動(dòng)并分析腦網(wǎng)絡(luò)功能連接的研究。研究方法:將40只大鼠隨機(jī)分成兩組,經(jīng)立體定向注射6-ODHDA偏側(cè)造模(6-OHDAgroup,n=24)和等劑量生理鹽水(Shamgroup,n=16),隨后將兩組大鼠隨機(jī)分成兩組,分別進(jìn)行腹腔注射左旋多巴(L-DOPA)聯(lián)合芐絲肼和等劑量生理鹽水(saline)連續(xù)21天,每天一次。實(shí)驗(yàn)分為4組:6-OHDA+L-DOPA組,n=15;6-OHDA+saline 組,n=9;Sham+L-DOPA 組,n=8;Sham+saline 組,n=8,記錄清醒、自由活動(dòng)的4組大鼠每次打藥后3小時(shí)內(nèi)dStr和SNr局部場(chǎng)電位活動(dòng),分析功率譜密度(Power spectral density),相干性(coherence)和格蘭杰因果分析(Granger causality analysis)。隨后探討5-HT自受體激動(dòng)劑依托拉嗪(eltoprazine)對(duì)LID行為學(xué)以及電生理影響,將6-OHDA+L-DOPA組隨機(jī)分成兩組,6-OHDA+L-DOPA+Elto 組,n=9;6-OHDA+L-DOPA+saline 組,n=6,分析兩組LID大鼠行為學(xué)和上述電生理變化。研究結(jié)果:相比于Sham+L-DOPA組,腹腔注射6-OHDA+L-DOPA組dStr和SNr的5-8Hz功率譜密度顯著增強(qiáng),二者5-8Hz相干性系數(shù)顯著增強(qiáng);相比與 Sham+saline 組,6-ODHA+saline 組 24-36Hz 功率譜密度增強(qiáng),二者 24-36Hz相干性顯著性增強(qiáng);6-OHDA +L-DOPA組dStr和SNr增強(qiáng)的5-8Hz振蕩電活動(dòng)與L-DOPA注藥后3小時(shí)內(nèi)不同時(shí)間點(diǎn)的AIMs評(píng)分成正相關(guān)關(guān)系,與1-21天左旋多巴注藥后AIMs評(píng)分未見相關(guān)性。6-OHDA+L-DOPA組中,SNr→dStr的5-8Hz格蘭杰因果系數(shù)顯著高于Sham+L-DOPA組;6-ODHA+saline組中,dStr→SNr的24-36Hz格蘭杰因果系數(shù)顯著高于Sham+saline組。腹腔注射5-HT自受體激動(dòng)劑依托拉嗪(eltoprazine)顯著降低6-OHDA+L-DOPA組AIMs評(píng)分、功率譜密度、相干性系數(shù)、格蘭杰因果系數(shù)。研究結(jié)論:自由活動(dòng)狀態(tài)下LID大鼠SNr和dStr的θ頻段(5-8Hz)振蕩電活動(dòng)顯著增高,并且兩部位θ振蕩具有相干性。這種增高的θ頻段振蕩電活動(dòng)與LID大鼠單次打藥后3小時(shí)以內(nèi)不同時(shí)間點(diǎn)的AIMs評(píng)分成正相關(guān)。增強(qiáng)的θ頻段的電活動(dòng)在SNr和dStr兩部位之間信息流動(dòng)的方向?yàn)镾Nr→dStr,增強(qiáng)的24-36Hz頻段的電活動(dòng)在SNr和dStr兩部位之間信息流動(dòng)的方向?yàn)閐Str→SNr,提示在LID狀態(tài)下,SNr的θ振蕩電活動(dòng)起主導(dǎo)作用,可能是θ振蕩電活動(dòng)的源頭。相反,在PD狀態(tài)下,dStr的β振蕩電活動(dòng)起主導(dǎo)作用。5-HT自受體激動(dòng)劑依托拉嗪能夠降低LID大鼠行為學(xué)評(píng)分,同時(shí)降低增強(qiáng)的5-8Hz頻段振蕩電活動(dòng),并且θ振蕩電活動(dòng)在SNr和dStr之間信息流動(dòng)的方向也隨之下降。說明5-HT系統(tǒng)不僅參與LID病例生理機(jī)制,同時(shí)可能是通過調(diào)節(jié)基底節(jié)θ振蕩電活動(dòng)改善LID非隨意運(yùn)動(dòng)癥狀。
[Abstract]:Objective: Levodopa induced dyskinesia was induced by levodopa. Lidis is a common disabling complication in patients with advanced Parkinson disease (PD). The pathogenesis of dyskinesia has not been elucidated at present. Local field potential is recorded in local field potential. LFP is an important method to study the electrophysiological mechanism of PD and its motor complication LID. The dorsolateral striatum was recorded in the dorsolateral striatum of the basal ganglia of LID rats. D Strand and substantia nigra pars reticulate. Methods: forty rats were randomly divided into two groups. 6-OHDA group (6-OHDA group) and the same dose of normal saline were injected into the model by stereotactic injection of 6-ODHDA (6-OHDAgroupN) and the same dose of normal saline (ShamgroupN) 16). Then the rats in the two groups were randomly divided into two groups. The rats were given intraperitoneal injection of L-DOPA plus benzylhydrazine and saline for 21 days respectively. Once a day. The experiment was divided into 4 groups: 1: 6-OHDA-DOPA group (n = 15); 6-OHDA saline group; Sham L-DOPA group; In Sham saline group, the local field potentials of dStr and SNr were recorded within 3 hours after administration of dStr and SNr. Power spectral density was analyzed. Coherence and Granger causality analysis. Then we studied the 5-HT autoreceptor agonist etalazine. Effects of eltoprazine on LID behavior and electrophysiology. The 6-OHDA L-DOPA group was randomly divided into two groups: 6-OHDA L-DOPA Elto group. 6-OHDA L-DOPA saline group was used to analyze the behavioral and electrophysiological changes of LID rats in two groups. Results: compared with Sham L-DOPA group. In the 6-OHDA L-DOPA group, the 5-8Hz power spectral density of dStr and SNr was significantly increased, and the coherence coefficient of 5-8Hz was significantly enhanced in the 6-OHDA L-DOPA group. Compared with Sham saline group, the power spectral density of 6-ODHA saline group was increased, and the correlation between them was significantly enhanced. The 5-8Hz oscillatory activity enhanced by dStr and SNr in 6-OHDA L-DOPA group was positively correlated with the AIMs scores at different time points within 3 hours after L-DOPA injection. There was no correlation with the AIMs score of 1-21 days after L-DOPA injection. 6-OHDA L-DOPA group. 鈫扵he 5-8Hz Granger causality coefficient of dStr is significantly higher than that of Sham L-DOPA 6-ODHA saline. 鈫扵he 24-36Hz Granger causality coefficient of SNr was significantly higher than that of Sham saline. The AIMs score of 6-OHDA L-DOPA group was significantly decreased. Power spectral density, coherence coefficient, Granger causality coefficient. Conclusion: the oscillatory electrical activity of SNr and dStr in SNr and dStr in free activity state is significantly increased. This increased 胃 band oscillatory electrical activity was positively correlated with the AIMs score at different time points within 3 hours after single drug administration in LID rats. The direction of information flow between SNr and dStr is SNr. 鈫扗Str, enhanced 24-36Hz electrical activity between SNr and dStr flows in the direction of dStr. 鈫扴NR, which indicates that the 胃 oscillatory activity of SNR plays a leading role in the LID state, and may be the source of theta oscillatory activity. On the contrary, in PD state. The 尾 -oscillatory electrical activity of dStr plays a leading role. 5-HT self-receptor agonist etalazine can reduce the behavioral score of LID rats and decrease the enhanced oscillatory activity in 5-8Hz band. The direction of information flow between SNr and dStr also decreased, indicating that 5-HT system is not only involved in the physiological mechanism of LID cases. At the same time, it may be by regulating the basal ganglia 胃 oscillatory electrical activity to improve LID involuntary motion symptoms.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R742.5;R-332

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相關(guān)期刊論文 前1條

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本文編號(hào)：1460954