帕金森病患者伴发疲劳的临床特点及潜在机制的研究

发布时间：2018-05-19 22:21

本文选题：帕金森病 + 疲劳　；参考：《首都医科大学》2014年硕士论文

【摘要】：目的探讨帕金森病（PD）患者伴发疲劳的临床特征、相关因素及潜在机制。方法收集2011年9月-2013年12月就诊于北京天坛医院神经内科的315例PD患者，进行如下研究： 1、采用疲劳评定量表及疲劳严重度量表、运动症状及非运动症状相关量表评价PD患者的临床特征采用疲劳评定量表-14（FS-14）、疲劳严重度量表（FSS）评价PD患者疲劳的临床特征，采用运动症状及非运动症状相关量表评价PD患者的运动及非运动症状，将疲劳评分分别与运动及非运动症状的评分进行相关性分析。 2、检测PD患者脑脊液病理相关蛋白的水平，研究其与疲劳评分的关系检测PD患者脑脊液α-突触核蛋白寡聚体、β-淀粉样蛋白1-42（Aβ1-42）、总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，并与疲劳评分进行相关性分析。 3、检测PD患者脑脊液神经递质的水平，研究其与疲劳评分的关系检测PD患者脑脊液多巴胺（DA）及其代谢产物3，4二羟基苯乙酸（DOPAC）及高香草酸（HVA）、去甲肾上腺素（NE）、5-羟色胺（5-HT）和乙酰胆碱（Ach）的水平，并与疲劳评分进行相关性分析。 4、检测PD患者血清及脑脊液铁及铁代谢相关蛋白的水平，研究其与疲劳评分的关系检测PD患者血清及脑脊液铁（Iron）、铁蛋白(Fer)、重链铁蛋白（H-Fer）、轻链铁蛋白（L-Fer）、转铁蛋白（Tf)、转铁蛋白受体（TfR）、乳铁蛋白（Lf）、膜铁转运蛋白1（FP1）、二价金属转运蛋白（DMT1）和铜蓝蛋白（CP）的水平，并与疲劳评分进行相关性分析。 5、检测PD患者血清及脑脊液神经免疫炎性因子的水平，研究其与疲劳评分的关系检测PD患者血清及脑脊液过氧化氢（H2O2）、一氧化氮（NO）、白介素-1β（IL-1β）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、可溶性肿瘤坏死因子-α受体1（sTNF-αR1）、总超氧化物歧化酶(tSOD)、干扰素γ（γ-INF)及前列腺素E2（PGE2）的水平，并与疲劳评分进行相关性分析。结果 1、PD伴发疲劳的临床特征（1）在315例PD患者中，197例患者伴发疲劳症状，占62.54%为疲劳组；118例PD患者不伴发疲劳症状，占37.46%，为非疲劳组。疲劳组患者的总体疲劳、疲劳严重度评分明显高于非疲劳组，分别为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）与非疲劳组相比，疲劳组的H-Y分期、UPDRS Ⅲ总分均明显高于非疲劳组，分别为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患者总体疲劳、疲劳严重度评分与焦虑评分呈显著的正相关（r=2.800、2.050，P0.05）。 2、PD疲劳组患者脑脊液病理相关蛋白的水平与疲劳的关系 PD疲劳组疲劳严重度评分与脑脊液Aβ1-42水平呈显著的负相关（r=-0.293，P0.05）；PD疲劳组疲劳严重度评分与脑脊液P-tau (T231)水平呈显著的正相关（r=0.592，P0.05）。 3、PD疲劳组患者脑脊液神经递质的水平与疲劳的关系 PD疲劳组脑脊液各神经递质的水平与疲劳评分无显著相关性。 4、PD疲劳组患者铁及铁代谢相关蛋白的水平及其与疲劳的关系（1）PD疲劳组患者脑脊液铁及铁代谢相关蛋白的水平与疲劳的关系 PD疲劳组疲劳严重度评分与脑脊液中CP、DMT1及Lf的水平均呈显著的正相关（r=0.571、0.358和0.359，P＜0.05）；总体疲劳评分与脑脊液中Tf的水平呈显著的正相关（r=0.298，P＜0.05）。（2）血清铁及铁代谢相关蛋白水平与疲劳评分的关系 PD疲劳组患者疲劳严重度评分与Tf的水平呈显著的负相关（r=-0.275，P＜0.05）。 5、PD疲劳组患者血清及脑脊液神经免疫炎性因子的水平与疲劳评分的关系（1）PD疲劳组患者脑脊液神经免疫炎性因子水平与疲劳评分的关系 PD疲劳组患者总体疲劳评分与脑脊液sTNF-αR1水平呈显著的正相关（r=0.363，P＜0.05）。（2）PD疲劳组患者血清神经免疫炎性因子水平与疲劳评分的关系 PD疲劳组患者疲劳严重度评分与血清t SOD水平呈显著的正相关（r=0.235，P＜0.05）。结论 1、PD患者疲劳的发病率高，焦虑是疲劳的独立危险因素。 2、PD伴发疲劳患者脑内存在Aβ1-42及P-tau(T231)的沉积，对认知功能的下降有预测作用。 3、PD伴发疲劳患者存在中枢及外周铁代谢紊乱，促进铁在脑内沉积。 4、PD伴发疲劳患者总体疲劳与脑脊液sTNFα R1水平呈显著的正相关，推测其可能通过神经免疫炎症机制损伤与疲劳相关的脑区，从而导致疲劳的发生。 5、PD伴发疲劳患者疲劳严重度评分与血清中t SOD水平呈显著的正相关，表明PD伴发疲劳患者早期可能通过增强抗氧化能力，实现对神经元的保护作用。
[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.
【学位授予单位】：首都医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.5

【参考文献】