本文選題：睡眠呼吸暫停 + 阻塞性��； 參考：《山東大學(xué)》2011年碩士論文

【摘要】：背景：阻塞性睡眠呼吸暫停綜合征(obstructive sleep apnea syndrome, OSAS)能導(dǎo)致患者出現(xiàn)認(rèn)知障礙,據(jù)研究,患者出現(xiàn)認(rèn)知障礙的發(fā)生機(jī)制主要和慢性、反復(fù)性、可逆性的夜間低氧與睡眠結(jié)構(gòu)紊亂有關(guān)。缺氧敏感區(qū)腦組織的病理生理改變可能就是OSAS患者產(chǎn)生認(rèn)知障礙的病理基礎(chǔ)。有關(guān)研究表明,OSAS患者的認(rèn)知障礙表現(xiàn)為全面的認(rèn)知功能缺損,并且可能與老年癡呆癥(senile dementia, SD)有一定的相關(guān)性。隨著科技的發(fā)展,神經(jīng)影像技術(shù)等檢查方法的進(jìn)步和應(yīng)用,增加了對(duì)OSAS患者認(rèn)知功能的評(píng)估手段,但仍然不夠完善,仍有待建立一套特異性高、可操作性強(qiáng)的臨床評(píng)價(jià)體系。阿爾茨海默病相關(guān)神經(jīng)絲蛋白(Alzheimer-associated neuronalthread protein, AD7c-NTP)是神經(jīng)絲蛋白家族中的一個(gè)成員,它在神經(jīng)元中表達(dá),并定位于生發(fā)神經(jīng)細(xì)胞的軸突,在早期或中度SD患者的皮層神經(jīng)元、腦組織抽提物、腦脊液中都有升高,并且其含量與癡呆的嚴(yán)重程度成正比。國外有關(guān)研究發(fā)現(xiàn),檢測(cè)SD患者尿樣中AD7c-NTP能達(dá)到與檢測(cè)腦脊液中其含量同樣的效果。尿中AD7c-NTP的檢測(cè)作為一種無創(chuàng)性的檢查更容易被患者接受,也更易于在臨床上推廣。血清淀粉樣蛋白A (serum amyloid A protein, SAA)是人體主要急性時(shí)相蛋白之一,受炎性細(xì)胞因子的正性調(diào)節(jié),這些炎性細(xì)胞因子包括白細(xì)胞介素-1(IL-1)和白細(xì)胞介素-6(IL-6)等。SAA主要由肝臟合成,并且以高密度脂蛋白(HDL)顆粒中載脂蛋白的一種主要成分分泌。SAA可以在SD患者的大腦中積聚,此現(xiàn)象可能與慢性大腦炎癥有關(guān),并且可能導(dǎo)致神經(jīng)元的損耗和白質(zhì)的損傷。OSAS患者血清中SAA濃度的持續(xù)升高有助于解釋OSAS患者心血管疾病及癡呆發(fā)病率增加的原因。簡(jiǎn)易精神狀態(tài)量表(Mini-Mentalstat Examination, MMSE)可做簡(jiǎn)單的智力狀態(tài)檢查,評(píng)價(jià)所采取干預(yù)措施的療效,MMSE是認(rèn)知檢查中最常用的一個(gè)量表,它可以評(píng)價(jià)受試者的方位定向、計(jì)算力、短時(shí)記憶、語言復(fù)述、視覺空間認(rèn)知、結(jié)構(gòu)模仿以及執(zhí)行能力。MMSE包括：①方位定向力：時(shí)間定向力(5分)和地點(diǎn)定向力(5分)；②短時(shí)記憶力：即刻記憶力(3分)；延遲回憶力(3分)；③語言能力：命名(2分)、復(fù)述(1分)、書寫(1分)；④視空間認(rèn)知能力(1分)；⑤執(zhí)行能力(4分)；⑥計(jì)算力(5分)。MMSE共計(jì)30分。 方法：依據(jù)2009年中華耳鼻咽喉--頭頸外科雜志編輯委員會(huì),中華醫(yī)學(xué)會(huì)耳鼻咽喉--頭頸外科學(xué)分會(huì)咽喉學(xué)組,關(guān)于阻塞性睡眠呼吸暫停綜合征的診斷依據(jù),選擇2009年5月至2010年10月在山東大學(xué)第二醫(yī)院診斷為OSAS的門診或住院的患者,根據(jù)多導(dǎo)睡眠監(jiān)測(cè)(polysomnography, PSG)中的呼吸暫停低通氣指數(shù)(apnea-hypopnea index, AHI)的結(jié)果,將52例僅患OSAS的患者分為輕度OSAS組(n=11),中度OSAS組(n=12)和重度OSAS組(n=29)。另選18例在門診查體的年齡及體重指數(shù)(body mass index, BMI)與實(shí)驗(yàn)組相匹配的健康者作為對(duì)照組。以AD7c-NTP及SAA酶聯(lián)免疫吸附法(enzyme-linked immunosorbent assays, ELISA)測(cè)定和比較各組間晨尿AD7c-NTP及上午6：00時(shí)的血清SAA濃度。此外,將OSAS患者的AD7c-NTP, SAA水平分別與AHI和最低血氧飽和度(the lowest arterial oxygen saturation, LSaO2)作相關(guān)性分析。正常組、實(shí)驗(yàn)組及實(shí)驗(yàn)組應(yīng)用MMSE評(píng)價(jià)實(shí)驗(yàn)組與正常對(duì)照組的認(rèn)知功能差別以及實(shí)驗(yàn)組經(jīng)3個(gè)月的持續(xù)正壓通氣治療(continuous positive airways pressure, CPAP)前后的認(rèn)知功能差別。所有數(shù)據(jù)均經(jīng)SPSS 17.0 for windows軟件進(jìn)行統(tǒng)計(jì)學(xué)處理,包括方差齊性檢驗(yàn)、t檢驗(yàn),以及相關(guān)性分析等。 結(jié)果：各組間年齡、體重指數(shù)無顯著差異,但多導(dǎo)睡眠監(jiān)測(cè)指標(biāo)AHI, LSaO2組間差異非常顯著(P0.01),并隨OSAS患者程度的加重而增高。正常對(duì)照組AD7c-NTP、SAA濃度分別是(1.56±0.67) ng/ml、(6.22±2.63μg/ml),與此相比,實(shí)驗(yàn)組AD7c-NTP在輕度組無明顯升高、但SAA濃度在輕度組就明顯升高,AD7c-NTP為1.63±0.87 n g/ml (P=0.4)、SAA為11.13±3.41μg/ml (P 0.05);中度OSAS組AD7c-NTP為2.06±0.64 n g/ml (P0.05), SAA為18.37±1.17μg/ml (P0.01);重度OSAS組AD7c-NTP為2.20±0. 83 n g/ml (P0.005), SAA為23.76±2.94μg/ml (P 0.01)。OSAS各組間AD7c-NTP、SAA濃度亦有顯著差異。OSAS各組患者尿液AD7c-NTP含量與其AHI呈顯著正相關(guān),其相關(guān)系數(shù)r為0.48(P0.05)；與夜間LSaO,呈顯著負(fù)相關(guān),其相關(guān)系數(shù)r為-0.56(P0.05)。相關(guān)性分析還顯示OSAS患者SAA濃度與AHI呈顯著正相關(guān),相關(guān)系數(shù)r為0.90(P0.001),與LSaO,之間呈顯著負(fù)相關(guān),相關(guān)系數(shù)r為-0.85(P0.001)。實(shí)驗(yàn)組與正常對(duì)照組之間及實(shí)驗(yàn)組經(jīng)CPAP治療前后的定向力(時(shí)間定向力和地點(diǎn)定向力)、記憶力(即刻記憶力、延遲回憶力)、語言能力(命名、復(fù)述、書寫；視空間能力)、執(zhí)行能力、計(jì)算力均無明顯統(tǒng)計(jì)學(xué)差異(P0.05)。 結(jié)論：OSAS患者尿液AD7c-NTP及血清SAA濃度較正常對(duì)照組顯著增高,且與OSAS的嚴(yán)重程度相關(guān)。AD7c-NTP及SAA濃度的升高可能與OSAS患者罹患老年癡呆癥的高危狀態(tài)有關(guān)。實(shí)驗(yàn)組與正常對(duì)照組相比較及實(shí)驗(yàn)組經(jīng)3個(gè)月的CPAP治療前后智能精神狀態(tài)無明顯統(tǒng)計(jì)學(xué)差異,分析可能與患病和(或)治療時(shí)間過短以及MMSE作為認(rèn)知功能減退的隨訪工具亦不夠敏感所致。
[Abstract]:Background: obstructive sleep apnea syndrome (OSAS) can cause cognitive impairment in patients. According to the study, the pathogenesis of cognitive impairment is mainly and chronic, the recurrent, reversible nocturnal hypoxia is related to the disorder of sleep structure. The pathophysiological changes in the brain tissue in the hypoxic sensitive area may be altered. This is the pathological basis of cognitive impairment in patients with OSAS. Studies have shown that cognitive impairment in OSAS patients is characterized by comprehensive cognitive impairment and may be associated with Alzheimer's disease (senile dementia, SD). With the development of science and technology, the progress and application of the methods of neuroimaging techniques, such as neuroimaging techniques, have increased the incidence of OSAS. Alzheimer-associated neuronalthread protein (AD7c-NTP), a member of the neurofilament family, is a member of the neurofilament family, which is located in the neuron and is located in the neuron. The axons of the germinal nerve cells were increased in the cortical neurons, brain tissue extracts and cerebrospinal fluid in the early and moderate SD patients, and their content was proportional to the severity of the dementia. Foreign related studies abroad found that the same effect of AD7c-NTP in the urine samples of patients with SD was detected. Urine AD7c-NTP was detected in the urine. As a noninvasive test, it is easier to be accepted by the patient and is more likely to be popularized in clinical. Serum amyloid A (serum amyloid A protein, SAA) is one of the major acute phase proteins in the human body, and is regulated by the positive regulation of inflammatory cytokines, including interleukin -1 (IL-1) and interleukin -6 (IL-6). .SAA, which is mainly synthesized by the liver and secreted by a major component of the apolipoprotein (HDL) particles in the high density lipoprotein (HDL) particles, can accumulate in the brain of the patients with SD, which may be associated with chronic inflammation of the brain and may lead to the loss of neurons and the damage of white matter to the sustained increase in the concentration of SAA in the serum of.OSAS patients. The reasons for the increase in the incidence of cardiovascular disease and dementia in OSAS patients are explained. Simple mental state scale (Mini-Mentalstat Examination, MMSE) can be used for a simple mental state examination to evaluate the effectiveness of the intervention measures. MMSE is the most commonly used scale in cognitive examination. It can evaluate the orientation, calculation, and short time of the subjects. Memory, language rehearsal, visual spatial cognition, structural imitation, and executive ability.MMSE include: (1) orientation force (5 points) and location orientation (5); second time memory: immediate memory (3); delayed memory (3); language power: naming (2), rehearsal (1), 1); (4) visual spatial cognition Ability (1 points); execution ability (4 points); calculation power (5 points).MMSE total 30 points.
Methods: according to the 2009 Chinese Otorhinolaryngology, the editorial board of the Journal of head and neck surgery, the pharyngology group of the Chinese Medical Association of Otolaryngology, head and neck surgery branch, on the diagnosis of obstructive sleep apnea syndrome, selected outpatients or hospitalized patients who were diagnosed as OSAS in Second Hospital of Shandong University from May 2009 to October 2010. According to the results of the apnea hypopnea index (apnea-hypopnea index, AHI) in polysomnography (PSG), 52 patients with OSAS were divided into mild OSAS group (n=11), moderate OSAS group (n=12) and severe OSAS group (n=29). The age and body mass index of 18 cases in the outpatient examination were selected as the experimental group. The matched healthy subjects were used as the control group. The serum SAA concentration was measured and compared between the morning urine AD7c-NTP and the serum SAA at 6:00 a.m. by AD7c-NTP and SAA enzyme linked immunosorbent assay (enzyme-linked immunosorbent assays, ELISA). The AD7c-NTP, SAA level of the OSAS patients were respectively compared with AHI and minimum oxygen saturation. Uration, LSaO2) for correlation analysis. The cognitive function differences between the normal group, the experimental group and the experimental group were used to evaluate the cognitive function of the experimental group and the normal control group and the experimental group after 3 months of continuous positive pressure ventilation (continuous positive airways pressure, CPAP). All the data were carried out by the SPSS 17 for Windows software. Statistical analysis including homogeneity test, t test and correlation analysis were conducted.
Results: there was no significant difference in age and body mass index among all groups, but the polysomnography index AHI, LSaO2 group was very significant (P0.01), and increased with the severity of OSAS. The concentration of AD7c-NTP and SAA in the normal control group was (1.56 + 0.67) ng/ml, respectively, (6.22 + 2.63 mu g/ml). Compared with this, the experimental group had no obvious rise in the mild group. But the concentration of SAA was significantly higher in the mild group, AD7c-NTP was 1.63 + 0.87 n g/ml (P=0.4), SAA was 11.13 + 3.41 mu g/ml (P 0.05), and AD7c-NTP in the moderate OSAS group was 2.06 + 0.64 n g/ml, and 18.37 + 1.17 micron. The concentrations of c-NTP and SAA were also significantly different in the urine AD7c-NTP content in.OSAS groups, and the correlation coefficient was 0.48 (P0.05), and the correlation coefficient was negatively correlated with night LSaO, and the correlation coefficient r was -0.56 (P0.05). The correlation analysis also showed that the concentration of the OSAS patients was positively correlated with the LSaO, and the correlation coefficient was 0.90. There was a significant negative correlation between O, and the correlation coefficient r was -0.85 (P0.001). In the experimental group and between the normal control group and the experimental group, the directional force (time orientation and location orientation), memory (immediate memory, delayed recall), language ability (naming, rehearsal, writing; visual space), execution ability and computational power were not obvious between the experimental group and the normal control group and the experimental group before and after the treatment of CPAP. Statistical difference (P0.05).
Conclusion: the concentration of urine AD7c-NTP and serum SAA in OSAS patients was significantly higher than that in the normal control group, and the increase of.AD7c-NTP and SAA concentration associated with the severity of OSAS may be related to the high risk state of Alzheimer's disease in OSAS patients. The experimental group compared with the normal control group and the experimental group after 3 months of CPAP therapy in the mental state. There was no statistically significant difference between the two groups. The analysis may be due to the short duration of treatment and / or the lack of sensitivity of MMSE as a follow-up tool for cognitive decline.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R766.7

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