MCI合并失眠障碍患者血清H2S、NSE表达水平及其临床意义的研究

MCI合并失眠障碍患者血清H2S、NSE表达水平及其临床意义的研究(论文12000字,文献综述)
摘要
目的：研究MCI合并失眠障碍（Insomnia Disorder,ID）患者血清硫化氢 H2S和神经元特异性烯醇化酶NSE表达水平，综合评价H2S、NSE与失眠障碍及认知功能损伤的关联性。为MCI患者的病情进展及诊疗提供实验依据和可靠的手段。
方法：本研究共纳入研究对象96例，均为2015年10月至2016年10月南华大学第二附属医院门诊病人和体检对象。其中MCI组28名,MCI合并失眠组38名，对照组则由30名性别、年龄、受教育程度相匹配的健康体检者组成。采用一般状况问卷、MMSE、GDS、CDR、ADL、HIS、MoCA量表评价其认知功能，采用匹兹堡睡眠质量指数问卷（PSQI）以及多导睡眠图（PSG）评价失眠障碍临床特征；所有研究对象均取空腹左侧肘静脉血3ml, 4℃3000r/m 离心分离血清，采用去蛋白分光光度法检测硫化氢（H2S）含量，采用酶联免疫法对血清中的神经元特异性烯醇化酶NSE 含量进行测定。同时进行相关临床指标的检测及相关性分析。使用 SPSS21.0 统计分析软件进行统计分析。

结果：1.各组研究对象年龄、性别、教育年限及体重指数等基线期资料比较，差异均无统计学意义（P>0.05），说明三组之间具有可比性。
2. 与正常对照组比较，MCI组和MCI合并失眠组MMSE和MoCA得分均低于正常对照组，差异有统计学意义(p<0.05），而GDS、CDR、ADL得分均高于正常对照组，差异有统计学意义(p<0.01)。而与MCI组比较，MCI合并失眠组MMSE和MoCA得分均低、GDS得分高，差异有统计学意义(p<0.05)。
3. MCI合并失眠组与正常对照组及MCI组比较，在以 PSQI 评估的主观睡眠情况结果差异有统计学意义(p<0.01)，由PSG 结果比较可知，MCI合并失眠组清醒次数（awakingtimes, AT）、入睡后清醒时间、REM 潜伏期均高于其它两组，差异有统计学意义(p<0.05)。
4.与对照组相比，MCI组以及MCI合并失眠组的H2S总体水平降低，差异有统计学意义（p<0.01）；而MCI组表达稍高于MCI合并失眠组，两组内比较差异统计学意义（P<0.05）。与对照组相比， MCI组以及MCI合并失眠组NSE的整体水平升高，差异有统计学意义（p<0.05和p<0.01）；而MCI组表达低于合并失眠组，两组内比较差异有统计学意义（P<0.05）。
5.MCI合并失眠患者H2S分别与MoCA、MMSE呈正相关，与PSQI呈负相关。血清 NSE 水平分别与MoCA、MMSE呈负相关，与PSQI呈正相关。
6.血清H2S和NSE含量用于诊断MCI的Cut Off值分别为24.065μmol/L、34.174 pg/ml。
结论：
1.MCI合并失眠患者认知功能较单纯MCI患者差，说明失眠是诱发或加重MCI认知障碍的程度的一个危险因素。
2. MCI患者的血清 H2S水平降低，且与认知损害、睡眠状况的严重程度相关，提示H2S可能是MCI合并失眠脑损伤保护的重要靶点之一。
3. 检测血清 H2S和 NSE水平变化对MCI的诊断、严重程度及尽早干预有重要意义。

关键词：轻度认知障碍；失眠症；硫化氢；神经元特异性烯醇化酶；临床意义

Study on the expression of H2S and NSE level and clinical significance in Insomnia patients with MCI
Abstract
Objective:To detect the expression of H2S and NSE in Insomniapatients with MCI,To evaluate H2S and NSE association with insomnia disorder and cognitive impairment,MCI patients with disease progression and diagnosis provide experimental evidence and reliable means.
Methods:A total of 96 study subjects were enrolled in this study, both outpatients and physical examination subjects of the Second Affiliated Hospital of Nanhua University from October 2015 to October 2016. Among them, 28 were in the MCI group and 38 were in the MCI combined with insomnia group. The control group consisted of 30 healthy subjects with matched sex, age and education level. The general condition questionnaire, MMSE, GDS, CDR, ADL, HIS and MoCA scale were used to evaluate their cognitive function. Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were used to evaluate the clinical features of insomnia. Serum samples were collected from 3 ml elbow venous blood on the left side of the left ventricle and centrifuged at 3000 r / m at 4 ℃. The content of hydrogen sulfide (H2S) was determined by deproteinization spectrophotometry. Serum levels of neuron-specific enolase NSE Content was measured. At the same time, the detection of related clinical indicators and correlation analysis. Use SPSS21.0 statistical analysis software for statistical analysis.
Results:1. The data of age, sex, years of education and body mass index were not significantly different among the three groups (P > 0.05), indicating the comparability among the three groups.
2.    Compared with the normal control group, MMSE and MoCA scores in MCI group and MCI combined insomnia group were lower than those in normal control group, the difference was statistically significant (p <0.05). The scores of GDS, CDR and ADL were higher than those of normal control group (p <0.01). Compared with MCI group, MCI combined insomnia group MMSE and MoCA scores were low, GDS score was high, the difference was statistically significant (p <0.05).
3.    Compared with the normal control group and the MCI group, there was significant difference in the subjective sleep status assessed by PSQI between the MCI combined insomnia group and the MCI group (p <0.01). Compared with the PSG results, the awaking times (AT) , Wakefulness after falling asleep, and REM latency were higher than the other two groups, the difference was statistically significant (p <0.05).
4.Compared with the control group, the overall level of H2S decreased in MCI group and MCI combined insomnia group, the difference was statistically significant (p <0.01); while the expression of MCI group was slightly higher than MCI combined with insomnia group, the difference was statistically significant (P <0.05). Compared with the control group, the overall level of NSE in MCI group and MCI combined with insomnia group was significantly increased (p <0.05 and p <0.01), while the expression of MCI group was lower than that of combined insomnia group There was statistical significance (P <0.05).
5. H2S in MCI patients with insomnia was positively correlated with MoCA and MMSE, and negatively correlated with PSQI. Serum NSE levels were negatively correlated with MoCA and MMSE, respectively, and positively correlated with PSQI.
6. The ratio of plasma H 2S and NSE was used to diagnose MCI, and the Cut Off （Checked the analyte）value was 24.065 μ mol / L 0.72934.174 PG / ml, respectively.

Conclusion:1. Cognitive function of MCI patients with insomnia was worse than that of patients with simple MCI, indicating that insomnia was a risk factor to induce or aggravate the degree of cognitive impairment of MCIpatients.
2. The level of serum H2S decreased in patients with MCI, and with cognitive impairment, the severity of sleep related, suggesting that H2S may be one of the important targets of MCI combined with insomnia brain injury protection.
3.Detection of serum levels of H2S and NSE changes in the diagnosis of MCI, the severity and early intervention is important.
Keywords:Mild Cognitive Impairment;Insomnia Iisorder ;Hydrogen Sulfide ;Neuron specific enolase ;Clinical significance ;

主要英文缩略语索引
缩写    英文全称    中文名称
ID    Insomnia  Disorder    失眠障碍
MCI    Mild  Cognitive impatirment    轻度认知功能障碍
MMSE    Minimengtal State Examination    简易智力状态检查量表
ADL    Activity of Daily Living Scale    日常生活能力量表
GDS    The Geriatric Depression Scale    老年抑郁量表
CDR    Clinical Dementia Rating    临床痴呆评定量表
HIS    Hachiski Ischemic Score    哈金斯缺血指数量表
MoCA    Montreal Cognitive Assessment Scale    蒙特利尔认知评估量表
PSQI    Pittsburgh Sleep Quality Index    匹茨堡睡眠质量指数
PSG    Polysomnogram    多导睡眠图
AT    Awakingtimes    清醒次数
REM    Rapid Eye Movement    快速眼动相
       
目    录
摘要....................................................
Abstract................................................
绪论....................................................
第一部分 材料与方法.....................................
1.1临床资料...........................................
1.1.1一般资料.....................................
1.2 相关标准..........................................
1.2.1 诊断标准....................................
1.2.2 排除标准....................................
1.3 仪器与试剂........................................
    1.3.1主要仪器....................................
    1.3.2主要试剂....................................
1.4 实验方法.........................................
      1.4.1资料收集....................................
      1.4.2认知损伤的评价..............................
      1.4.3睡眠障碍的评价..............................
      1.4.4血清H2S、NSE标本的收集与处理...............
1.4.5 H2S测定方法................................
      1.4.6血清NSE浓度测定...........................
1.5统计学方法.......................................
第二部分 结果与分析...................................
2.1一般资料.........................................
2.2研究对象认知功能比较分析.........................
2.3研究对象睡眠情况分析.............................
2.4血清中H2S及NSE分析.............................
2.5血清标志物（H2S、NSE）与睡眠状况、认知功能的相关性..
2.6诊断MCI的生物学指标.............................
第三部分 讨论..........................................
3.1认知与睡眠的相关性.................................
 3.1.1正常衰老过程中睡眠的变化.......................
 3.1.2正常老年人睡眠障碍与认知功能的关系.............
 3.1.3睡眠障碍是MCI或AD的危险因素..................
3.1.4 MCI患者睡眠障碍与认知功能的关系................
3.2 H2S与脑损伤保护....................................
3.3 NSE与神经损伤.....................................
3.4 H2S和NSE在老年痴呆诊断中的价值...................
3.5本研究的局限和展望................................
第四部分 结论...........................................
参考文献...............................................
附录...................................................
综述...................................................