本文選題：阿爾茨海默病 + 基質(zhì)金屬蛋白酶2�。� 參考：《鄭州大學(xué)》2013年碩士論文

【摘要】：背景與目的 阿爾茨海默病(Alzheimer's disease, AD)是一種常見的中樞神經(jīng)系統(tǒng)退行性疾病,是癡呆的主要類型。國外最新的AD診斷標(biāo)準(zhǔn)的推薦指南中已納入了如Aβ、Tau蛋白等的生物學(xué)標(biāo)志物,說明生物學(xué)標(biāo)志物在AD診斷中的作用日益受到重視�；|(zhì)金屬蛋白酶(matrix metalloproteinases, MMPs)是一組鋅/鈣依賴的蛋白酶家族,主要參與細(xì)胞外基質(zhì)重組和修復(fù)。其中MMP-2(明膠酶A)和MMP-9(明膠酶B)與中樞神經(jīng)系統(tǒng)的關(guān)系密切,成為神經(jīng)系統(tǒng)疾病研究的熱點(diǎn)。近年有證據(jù)表明,MMPs有可能參與AD的發(fā)病,且有研究證實(shí)血清MMP-3水平與AD的嚴(yán)重程度相關(guān)。但目前尚無有關(guān)血清MMP-2、MMP-9水平與AD嚴(yán)重程度相關(guān)性的研究。本實(shí)驗(yàn)通過研究AD患者與正常對照組的血清MMP-2、MMP-9水平的變化,探討血清MMP-2、MMP-9與AD嚴(yán)重程度的相關(guān)性。研究對象與方法 正常對照組：鄭州大學(xué)第一附院醫(yī)院2012年10月健康體檢人員30例(男15例,女15例),年齡55歲～80歲,平均(68.2±6.1)歲。均根據(jù)病史、神經(jīng)和精神檢查、腦電圖、顱腦磁共振或CT檢查排除中樞神經(jīng)系統(tǒng)疾病及癡呆。 AD組：來自2011年8月～2012年12月入住鄭州大學(xué)第一附屬醫(yī)院及鄭州市郊的養(yǎng)老院的患者90例(男45例,女45例),年齡55-80歲,平均(65.4±8.5)歲。納入標(biāo)準(zhǔn)參照美國國立神經(jīng)病及語言交流障礙和卒中研究所(NINCDS)和Alzheimer病及相關(guān)疾病協(xié)會(ADRD A)推薦的臨床很可能AD診斷標(biāo)準(zhǔn)。根據(jù)MMSE評分將AD患者分為輕度、中度、重度組：21～26分的患者納入輕度AD組(30例),10～20分的患者納入中度AD組(30例),小于10分的患者納入重度AD組(30例)。 所有入組的受試者受教育程度均大于5年,分組均經(jīng)兩名以上神經(jīng)科醫(yī)師通過病史及相關(guān)標(biāo)準(zhǔn)而確定,均簽署知情同意書。 對受試者均在清晨空腹?fàn)顟B(tài)下采取肘靜脈血2ml置于以011mol/L枸櫞酸鈉1：9抗凝試管內(nèi),搖勻,離心取上清液,后置入EP管中,-80℃保存。采用雙抗體一步夾心法酶聯(lián)免疫吸附試驗(yàn)(ELISA)對標(biāo)本進(jìn)行檢測。 得出的數(shù)據(jù)應(yīng)用SPSS17.0統(tǒng)計(jì)學(xué)軟件進(jìn)行分析處理:對數(shù)據(jù)進(jìn)行正態(tài)性檢驗(yàn)和方差齊性檢驗(yàn),符合正態(tài)分布和方差齊性的數(shù)據(jù)以“均數(shù)±標(biāo)準(zhǔn)差”表示,多組間均數(shù)比較采用單因素方差分析,兩兩比較采用LSD-t檢驗(yàn),不符合正態(tài)分布的數(shù)據(jù)之間的比較采用Mann-Whitney U秩和檢驗(yàn)。檢驗(yàn)水準(zhǔn)取α=0.05。結(jié)果 1.AD組血清MMP-2和MMP-9水平與正常對照組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 2.AD不同嚴(yán)重程度組血清MMP-2和MMP-9水平不同。輕度組血清MMP-2和MMP-9水平與對照組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；中度組血清MMP-2和MMP-9水平與輕度組、對照組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；重度組血清MMP-2和MMP-9水平與對照組、輕度組、中度組比較,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。 3.AD患者血清MMP-2水平與MMP-9水平呈正相關(guān)(P0.05)。結(jié)論 1.隨著AD的病情加重,MMP-2、MMP-9水平亦隨之增高,MMP-2、MMP-9有可能參與了AD的發(fā)病。 2.AD患者血清MMP-2、MMP-9水平與AD疾病嚴(yán)重程度可能相關(guān),有可能成為AD診斷分級的參考指標(biāo)。
[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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R749.16

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