本文選題：帕金森病 + 疲勞��； 參考：《首都醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的 探討帕金森�。≒D）患者伴發(fā)疲勞的臨床特征、相關(guān)因素及潛在機(jī)制。方法 收集2011年9月-2013年12月就診于北京天壇醫(yī)院神經(jīng)內(nèi)科的315例PD患者，進(jìn)行如下研究： 1、采用疲勞評定量表及疲勞嚴(yán)重度量表、運(yùn)動癥狀及非運(yùn)動癥狀相關(guān)量表評價PD患者的臨床特征 采用疲勞評定量表-14（FS-14）、疲勞嚴(yán)重度量表（FSS）評價PD患者疲勞的臨床特征，采用運(yùn)動癥狀及非運(yùn)動癥狀相關(guān)量表評價PD患者的運(yùn)動及非運(yùn)動癥狀，將疲勞評分分別與運(yùn)動及非運(yùn)動癥狀的評分進(jìn)行相關(guān)性分析。 2、檢測PD患者腦脊液病理相關(guān)蛋白的水平，研究其與疲勞評分的關(guān)系 檢測PD患者腦脊液α-突觸核蛋白寡聚體、β-淀粉樣蛋白1-42（Aβ1-42）、總tau (T-tau)及不同部位磷酸化tau （P-tau），包括P-tau (T181)、P-tau (T231)、P-tau (S396)及P-tau (S199)的水平，并與疲勞評分進(jìn)行相關(guān)性分析。 3、檢測PD患者腦脊液神經(jīng)遞質(zhì)的水平，研究其與疲勞評分的關(guān)系 檢測PD患者腦脊液多巴胺（DA）及其代謝產(chǎn)物3，4二羥基苯乙酸（DOPAC）及高香草酸（HVA）、去甲腎上腺素（NE）、5-羥色胺（5-HT）和乙酰膽堿（Ach）的水平，并與疲勞評分進(jìn)行相關(guān)性分析。 4、檢測PD患者血清及腦脊液鐵及鐵代謝相關(guān)蛋白的水平，研究其與疲勞評分的關(guān)系 檢測PD患者血清及腦脊液鐵（Iron）、鐵蛋白(Fer)、重鏈鐵蛋白（H-Fer）、輕鏈鐵蛋白（L-Fer）、轉(zhuǎn)鐵蛋白（Tf)、轉(zhuǎn)鐵蛋白受體（TfR）、乳鐵蛋白（Lf）、膜鐵轉(zhuǎn)運(yùn)蛋白1（FP1）、二價金屬轉(zhuǎn)運(yùn)蛋白（DMT1）和銅藍(lán)蛋白（CP）的水平，并與疲勞評分進(jìn)行相關(guān)性分析。 5、檢測PD患者血清及腦脊液神經(jīng)免疫炎性因子的水平，研究其與疲勞評分的關(guān)系 檢測PD患者血清及腦脊液過氧化氫（H2O2）、一氧化氮（NO）、白介素-1β（IL-1β）、白介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）、可溶性腫瘤壞死因子-α受體1（sTNF-αR1）、總超氧化物歧化酶(tSOD)、干擾素γ（γ-INF)及前列腺素E2（PGE2）的水平，并與疲勞評分進(jìn)行相關(guān)性分析。 結(jié)果 1、PD伴發(fā)疲勞的臨床特征 （1）在315例PD患者中，197例患者伴發(fā)疲勞癥狀，占62.54%為疲勞組；118例PD患者不伴發(fā)疲勞癥狀，占37.46%，為非疲勞組。 疲勞組患者的總體疲勞、疲勞嚴(yán)重度評分明顯高于非疲勞組，分別為11.00（8.00，13.00）vs.6.00(4.00，9.00)分和5.67(4.89，6.67)vs.2.17(1.56，3.44)分（P0.05）。 （2）與非疲勞組相比，疲勞組的H-Y分期、UPDRS Ⅲ總分均明顯高于非疲勞組，分別為2.19±0.83vs.1.79±0.73期;26.50(18.75，35.75)vs.21.00(13.88，，31.00)分（P0.05）。 （3、）PD患者總體疲勞、疲勞嚴(yán)重度評分與焦慮評分呈顯著的正相關(guān)（r=2.800、2.050，P0.05）。 2、PD疲勞組患者腦脊液病理相關(guān)蛋白的水平與疲勞的關(guān)系 PD疲勞組疲勞嚴(yán)重度評分與腦脊液Aβ1-42水平呈顯著的負(fù)相關(guān)（r=-0.293，P0.05）；PD疲勞組疲勞嚴(yán)重度評分與腦脊液P-tau (T231)水平呈顯著的正相關(guān)（r=0.592，P0.05）。 3、PD疲勞組患者腦脊液神經(jīng)遞質(zhì)的水平與疲勞的關(guān)系 PD疲勞組腦脊液各神經(jīng)遞質(zhì)的水平與疲勞評分無顯著相關(guān)性。 4、PD疲勞組患者鐵及鐵代謝相關(guān)蛋白的水平及其與疲勞的關(guān)系 （1）PD疲勞組患者腦脊液鐵及鐵代謝相關(guān)蛋白的水平與疲勞的關(guān)系 PD疲勞組疲勞嚴(yán)重度評分與腦脊液中CP、DMT1及Lf的水平均呈顯著的正相關(guān)（r=0.571、0.358和0.359，P＜0.05）；總體疲勞評分與腦脊液中Tf的水平呈顯著的正相關(guān)（r=0.298，P＜0.05）。 （2）血清鐵及鐵代謝相關(guān)蛋白水平與疲勞評分的關(guān)系 PD疲勞組患者疲勞嚴(yán)重度評分與Tf的水平呈顯著的負(fù)相關(guān)（r=-0.275，P＜0.05）。 5、PD疲勞組患者血清及腦脊液神經(jīng)免疫炎性因子的水平與疲勞評分的關(guān)系 （1）PD疲勞組患者腦脊液神經(jīng)免疫炎性因子水平與疲勞評分的關(guān)系 PD疲勞組患者總體疲勞評分與腦脊液sTNF-αR1水平呈顯著的正相關(guān)（r=0.363，P＜0.05）。 （2）PD疲勞組患者血清神經(jīng)免疫炎性因子水平與疲勞評分的關(guān)系 PD疲勞組患者疲勞嚴(yán)重度評分與血清t SOD水平呈顯著的正相關(guān)（r=0.235，P＜0.05）。 結(jié)論 1、PD患者疲勞的發(fā)病率高，焦慮是疲勞的獨立危險因素。 2、PD伴發(fā)疲勞患者腦內(nèi)存在Aβ1-42及P-tau(T231)的沉積，對認(rèn)知功能的下降有預(yù)測作用。 3、PD伴發(fā)疲勞患者存在中樞及外周鐵代謝紊亂，促進(jìn)鐵在腦內(nèi)沉積。 4、PD伴發(fā)疲勞患者總體疲勞與腦脊液sTNFα R1水平呈顯著的正相關(guān)，推測其可能通過神經(jīng)免疫炎癥機(jī)制損傷與疲勞相關(guān)的腦區(qū)，從而導(dǎo)致疲勞的發(fā)生。 5、PD伴發(fā)疲勞患者疲勞嚴(yán)重度評分與血清中t SOD水平呈顯著的正相關(guān)，表明PD伴發(fā)疲勞患者早期可能通過增強(qiáng)抗氧化能力，實現(xiàn)對神經(jīng)元的保護(hù)作用。
[Abstract]:objective
Objective to explore the clinical characteristics, related factors and underlying mechanisms of fatigue in patients with Parkinson's disease (PD).
We collected 315 PD patients who were admitted to the Department of Neurology of Beijing Tiantan Hospital from September 2011 to December. The following studies were carried out: -2013
1, using the fatigue rating scale and fatigue severity scale, motor symptoms and non motor symptoms scale to evaluate the clinical characteristics of PD patients.
-14 (FS-14) and fatigue scale (FSS) were used to evaluate the clinical characteristics of fatigue in PD patients. The exercise symptoms and non motor symptoms related scales were used to evaluate the movement and non motor symptoms of the patients in PD, and the correlation analysis between the fatigue scores and the evaluation of exercise and non motor symptoms was carried out.
2, detect the level of pathological protein in cerebrospinal fluid of PD patients, and study its relationship with fatigue score.
The levels of alpha synuclein oligomer, beta amyloid protein 1-42 (A beta 1-42), total tau (T-tau) and tau (P-tau) in different parts of the cerebrospinal fluid of PD patients were measured, including P-tau (T181), P-tau (T231), P-tau (S396) and T-tau, and correlated with the fatigue score.
3, detect the level of neurotransmitters in CSF of PD patients, and study their relationship with fatigue score.
The levels of dopamine (DA) and its metabolites, 3,4 two hydroxyphenylacetic acid (DOPAC) and high vanillin (HVA), norepinephrine (NE), 5- serotonin (5-HT) and acetylcholine (Ach) were detected in the cerebrospinal fluid of the patients with PD, and the correlation was analyzed with the fatigue score.
4, detect serum and cerebrospinal fluid iron and iron metabolism related protein levels in PD patients, and study their relationship with fatigue score.
The levels of serum and cerebrospinal fluid (Iron), ferritin (Fer), heavy chain ferritin (H-Fer), light chain ferritin (L-Fer), transferrin (Tf), transferrin receptor (TfR), lactoferrin (Lf), membrane iron transporter 1 (FP1), two valence metal transport egg white (DMT1) and ceruloprotein (CP) were measured, and the correlation analysis between PD patients and fatigue score was measured.
5, detect the level of neuroinflammatory factors in serum and cerebrospinal fluid of PD patients, and study their relationship with fatigue score.
The serum and cerebrospinal fluid (H2O2), nitric oxide (NO), interleukin -1 beta (IL-1 beta), interleukins -6 (IL-6), tumor necrosis factor - alpha (TNF- - alpha), soluble tumor necrosis factor - alpha receptor 1 (sTNF- alpha R1), total superoxide dismutase (tSOD), interferon gamma (gamma -INF) and prostaglandin, were detected and compared with fatigue scores. The analysis of customs.
Result
1, the clinical characteristics of PD associated fatigue
(1) of the 315 PD patients, 197 patients had fatigue symptoms, accounting for 62.54% of the fatigue group, and 118 of the PD patients without fatigue symptoms, accounting for 37.46%.
The total fatigue and fatigue severity score of the patients in the fatigue group were significantly higher than those in the non fatigue group, which were 11 (8.00,13.00) vs.6.00 (4.00,9.00) and 5.67 (4.89,6.67) vs.2.17 (1.56,3.44) (P0.05) respectively.
(2) compared with the non fatigue group, the H-Y stage and UPDRS III total score of the fatigue group were significantly higher than those in the non fatigue group, which were 2.19 + 0.83vs.1.79 + 0.73 respectively, and 26.50 (18.75,35.75) vs.21.00 (13.88,31.00) (P0.05).
(3) there was a significant positive correlation between the overall fatigue and fatigue severity score of PD patients and the anxiety score (r=2.800,2.050, P0.05).
2, the relationship between the level of pathological protein in cerebrospinal fluid and fatigue in PD fatigue group.
There was a significant negative correlation between the fatigue severity score of PD fatigue group and the level of A beta 1-42 in cerebrospinal fluid (r=-0.293, P0.05), and the fatigue severity score of the PD fatigue group was positively correlated with the P-tau (T231) level in the cerebrospinal fluid (r=0.592, P0.05).
3, the relationship between the level of neurotransmitters in cerebrospinal fluid and fatigue in PD fatigue group
There was no significant correlation between the level of neurotransmitters in CSF and fatigue score in PD fatigue group.
4, the level of iron and iron metabolism related proteins in PD fatigue group and their relationship with fatigue.
(1) the relationship between the levels of iron and iron metabolism related proteins in cerebrospinal fluid and fatigue in patients with PD fatigue.
The fatigue severity score of PD fatigue group was significantly positively correlated with the levels of CP, DMT1 and Lf in cerebrospinal fluid (r=0.571,0.358 and 0.359, P < 0.05), and the overall fatigue score was positively correlated with the level of Tf in cerebrospinal fluid (r=0.298, P < 0.05).
(2) relationship between serum iron and iron metabolism related protein level and fatigue score
There was a significant negative correlation between fatigue severity score and Tf level in PD fatigue group (r=-0.275, P < 0.05).
5, the relationship between serum and cerebrospinal fluid levels of neuroinflammatory factors and fatigue scores in PD fatigue group
(1) the relationship between the level of neuroimmunologic inflammatory factors in cerebrospinal fluid and fatigue score in PD fatigue group
The overall fatigue score of PD fatigue group was significantly positively correlated with the level of sTNF- alpha R1 in cerebrospinal fluid (r=0.363, P < 0.05).
(2) relationship between serum levels of neuroimmunologic inflammatory factors and fatigue scores in PD fatigue group
There was a significant positive correlation between fatigue severity score and serum T SOD level in PD fatigue group (r=0.235, P < 0.05).
conclusion
1, the incidence of fatigue is high in PD patients, and anxiety is an independent risk factor for fatigue.
2, the deposition of A beta 1-42 and P-tau (T231) in the brain of PD patients with fatigue has a predictive effect on the decline of cognitive function.
3, there was central and peripheral iron metabolism disorder in PD patients with fatigue, which promoted iron deposition in the brain.
4, there is a significant positive correlation between total fatigue and sTNF alpha R1 level in cerebrospinal fluid in patients with PD associated fatigue. It is presumed that it may damage the brain area associated with fatigue through the mechanism of neuro immune inflammation, which leads to the occurrence of fatigue.
5, the fatigue severity score of PD associated fatigue patients has a significant positive correlation with the level of t SOD in the serum, indicating that the early fatigue patients with PD may have protective effects on the neurons by enhancing the antioxidant capacity.
【學(xué)位授予單位】：首都醫(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

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