阿尔茨海默病患者血清中基质金属蛋白酶2和9水平变化的临床研究

发布时间：2018-05-31 23:10

本文选题：阿尔茨海默病 + 基质金属蛋白酶2　；参考：《郑州大学》2013年硕士论文

【摘要】：背景与目的阿尔茨海默病(Alzheimer's disease, AD)是一种常见的中枢神经系统退行性疾病,是痴呆的主要类型。国外最新的AD诊断标准的推荐指南中已纳入了如Aβ、Tau蛋白等的生物学标志物,说明生物学标志物在AD诊断中的作用日益受到重视。基质金属蛋白酶(matrix metalloproteinases, MMPs)是一组锌/钙依赖的蛋白酶家族,主要参与细胞外基质重组和修复。其中MMP-2(明胶酶A)和MMP-9(明胶酶B)与中枢神经系统的关系密切,成为神经系统疾病研究的热点。近年有证据表明,MMPs有可能参与AD的发病,且有研究证实血清MMP-3水平与AD的严重程度相关。但目前尚无有关血清MMP-2、MMP-9水平与AD严重程度相关性的研究。本实验通过研究AD患者与正常对照组的血清MMP-2、MMP-9水平的变化,探讨血清MMP-2、MMP-9与AD严重程度的相关性。研究对象与方法正常对照组：郑州大学第一附院医院2012年10月健康体检人员30例(男15例,女15例),年龄55岁～80岁,平均(68.2±6.1)岁。均根据病史、神经和精神检查、脑电图、颅脑磁共振或CT检查排除中枢神经系统疾病及痴呆。 AD组：来自2011年8月～2012年12月入住郑州大学第一附属医院及郑州市郊的养老院的患者90例(男45例,女45例),年龄55-80岁,平均(65.4±8.5)岁。纳入标准参照美国国立神经病及语言交流障碍和卒中研究所(NINCDS)和Alzheimer病及相关疾病协会(ADRD A)推荐的临床很可能AD诊断标准。根据MMSE评分将AD患者分为轻度、中度、重度组：21～26分的患者纳入轻度AD组(30例),10～20分的患者纳入中度AD组(30例),小于10分的患者纳入重度AD组(30例)。所有入组的受试者受教育程度均大于5年,分组均经两名以上神经科医师通过病史及相关标准而确定,均签署知情同意书。对受试者均在清晨空腹状态下采取肘静脉血2ml置于以011mol/L枸橼酸钠1：9抗凝试管内,摇匀,离心取上清液,后置入EP管中,-80℃保存。采用双抗体一步夹心法酶联免疫吸附试验(ELISA)对标本进行检测。得出的数据应用SPSS17.0统计学软件进行分析处理:对数据进行正态性检验和方差齐性检验,符合正态分布和方差齐性的数据以“均数±标准差”表示,多组间均数比较采用单因素方差分析,两两比较采用LSD-t检验,不符合正态分布的数据之间的比较采用Mann-Whitney U秩和检验。检验水准取α=0.05。结果 1.AD组血清MMP-2和MMP-9水平与正常对照组比较,差异有统计学意义(P0.05)。 2.AD不同严重程度组血清MMP-2和MMP-9水平不同。轻度组血清MMP-2和MMP-9水平与对照组比较,差异有统计学意义(P0.05)；中度组血清MMP-2和MMP-9水平与轻度组、对照组比较,差异有统计学意义(P0.05)；重度组血清MMP-2和MMP-9水平与对照组、轻度组、中度组比较,差异均有统计学意义(P0.05)。 3.AD患者血清MMP-2水平与MMP-9水平呈正相关(P0.05)。结论 1.随着AD的病情加重,MMP-2、MMP-9水平亦随之增高,MMP-2、MMP-9有可能参与了AD的发病。 2.AD患者血清MMP-2、MMP-9水平与AD疾病严重程度可能相关,有可能成为AD诊断分级的参考指标。
[Abstract]:Background and purpose
Alzheimer's disease (AD) is a common degenerative disease of the central nervous system and is the main type of dementia. The recommended guidelines for the latest AD diagnostic criteria have been incorporated into the biological markers such as A beta, Tau protein and so on, indicating that the role of biomarkers in the diagnosis of AD is becoming more and more important. Matrix metalloproteinases (MMPs) is a group of zinc / calcium dependent protease families, which are mainly involved in the recombination and repair of extracellular matrix. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are closely related to the central nervous system and become a hot spot in the research of nervous system diseases. In recent years, there is evidence that MMPs may be involved in the pathogenesis of AD, And some studies have confirmed that serum MMP-3 level is related to the severity of AD. However, there is no study on the correlation between serum MMP-2, MMP-9 level and AD severity. The correlation between serum MMP-2, MMP-9 and AD severity in serum of AD patients and normal control group was investigated. The object and method of the study were studied.
The normal control group: 30 patients (15 males and 15 females) in the First Affiliated Hospital of Zhengzhou University (15 males and 15 females) in October 2012, the average age of 55 years to 80 years old (68.2 + 6.1) years, all according to the medical history, nerve and mental examination, electroencephalogram, craniocerebral magnetic resonance or CT examination to exclude central deity system disease and dementia.
Group AD: from August 2011 to December 2012, 90 patients (45 men, 45 women) were admitted to the First Affiliated Hospital of Zhengzhou University and the suburb of Zhengzhou. The average age was 55-80 years old (65.4 + 8.5). The standard referred to the national neuropathy and language communication disorder (NINCDS) and the Alzheimer disease and Related Diseases Association (ADR D A) recommended clinically possible AD diagnostic criteria. According to the MMSE score, AD patients were divided into mild, moderate, and severe groups: 21~26 points were included in the mild AD group (30 cases), 10~20 in the moderate AD group (30 cases), and less than 10 in the severe AD group (30 cases).
All the subjects were educated for more than 5 years, and the groups were all confirmed by the history and related standards by more than two neurologist and signed the informed consent.
The subjects were used in the morning empty stomach to take the elbow vein blood 2ml in the anticoagulant tube of 011mol/L sodium citrate 1:9, shake it evenly, take the supernatant by centrifugation, and then put it in the EP tube, and save it at -80. The specimens were detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA).
The data obtained by the SPSS17.0 statistics software are analyzed and processed: the data is tested by normality test and Fang Chaqi test, the data conforming to normal distribution and homogeneity of variance are expressed as "mean number + standard deviation", and the average number of multiple groups is compared with single factor variance analysis, and 22 is compared with LSD-t test, which does not conform to the normal distribution data. The Mann-Whitney U rank sum test was used to compare the results. The test result was obtained by a =0.05. result.
The serum levels of MMP-2 and MMP-9 in group 1.AD were significantly different from those in normal control group (P0.05).
The levels of serum MMP-2 and MMP-9 in the 2.AD group were different. The level of serum MMP-2 and MMP-9 in the mild group was statistically significant compared with the control group (P0.05). The level of serum MMP-2 and MMP-9 in the moderate group was compared with the mild group, and the difference was statistically significant (P0.05); the level of serum MMP-2 and MMP-9 in the severe group and the control group, the mild group, and the control group. The difference was statistically significant in moderate group (P0.05).
There was a positive correlation between serum MMP-2 level and MMP-9 level in 3.AD patients (P0.05).
1. with the aggravation of AD, the levels of MMP-2 and MMP-9 also increase. MMP-2 and MMP-9 may be involved in the pathogenesis of AD.
The serum MMP-2 and MMP-9 levels in patients with 2.AD may be correlated with the severity of AD disease, and may become a reference index for AD diagnostic grading.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16

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