本文選題：多系統(tǒng)萎縮 + NF-κB　； 參考：《大連醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:多系統(tǒng)萎縮(Multiple system atrophy,MSA)是一種病因不明,以帕金森樣癥狀、共濟(jì)失調(diào)和自主神經(jīng)功能紊亂為主的神經(jīng)系統(tǒng)變性疾病。本病的病理改變?yōu)閺V泛的神經(jīng)元缺失及神經(jīng)膠質(zhì)細(xì)胞增生。大量含嗜銀性纖維絲的少突膠質(zhì)細(xì)胞包涵體(Glial cytoplasmic inclusions,GCIs)形成是其病理學(xué)標(biāo)記。少突膠質(zhì)細(xì)胞包涵體主要包含錯誤折疊、高度磷酸化α-突觸核蛋白(α-synuclein,α-syn)。α-突觸核蛋白與神經(jīng)元退行性改變以及疾病進(jìn)程密切相關(guān),其異常表達(dá)受NF-κB信號轉(zhuǎn)導(dǎo)體系的調(diào)控。然而,NF-κB反應(yīng)體系的功能與細(xì)胞因子YKL-40(Chitinase3-Like-1,CHI3L1)和CD40的表達(dá)之間存在著復(fù)雜而密切的聯(lián)系。本研究主要探討多系統(tǒng)萎縮患者血清中YKL-40、CD40與健康人之間差異,以及其與多系統(tǒng)萎縮患者發(fā)病年齡、病程、疾病嚴(yán)重程度的相關(guān)性,為進(jìn)一步探求多系統(tǒng)萎縮的發(fā)病機(jī)制奠定基礎(chǔ),以期尋求具有多系統(tǒng)萎縮診斷價值的生物標(biāo)記物。方法:本研究中病例組為符合2008年修訂的Gilman診斷標(biāo)準(zhǔn)的多系統(tǒng)萎縮患者共30例(MSA-P型14例,MSA-C型16例),均為2013-2014年間大連醫(yī)科大學(xué)附屬第一醫(yī)院神經(jīng)內(nèi)科的住院患者。對照組為除外明確神經(jīng)系統(tǒng)疾病、腫瘤性疾病、炎癥性疾病和傳染性疾病的“健康人”30例。30例MSA患者均接受了統(tǒng)一多系統(tǒng)萎縮評定量表(Unified Multiple System Atrophy Rating Scale,UMSARS)第II部分評估。利用酶聯(lián)免疫吸附試驗(yàn)(Enzyme linked Immunosorbent Assay,ELISA)雙抗體夾心法檢測病例組和對照組血清中YKL-40與CD40濃度。多系統(tǒng)萎縮患者血清YKL-40、CD40濃度與“健康人”之間的差異進(jìn)行了統(tǒng)計學(xué)分析,并分析了其與多系統(tǒng)萎縮患者發(fā)病年齡、病程和UMSARS II評分之間的相關(guān)性。統(tǒng)計學(xué)分析采用SPSS13.0統(tǒng)計軟件包處理,設(shè)計顯著水平α為0.05。結(jié)果:病例組多系統(tǒng)萎縮患者共30例,其中MSA-P型14例,MSA-C型16例,分別占47%和53%,無明顯性別差異,平均發(fā)病年齡為59.43±10.04歲。病例組血清中YKL-40濃度為38.32(11.74)ng/ml,對照組為44.74±9.95 ng/ml,兩組間血清YKL-40濃度差異具有統(tǒng)計學(xué)意義(P=0.002),病例組血清YKL-40濃度明顯低于對照組。血清YKL-40水平與對照組年齡、性別無明顯相關(guān)性,與病例組多系統(tǒng)萎縮的臨床亞型(MSA-P型與MSA-C型)、發(fā)病年齡、病程和疾病嚴(yán)重程度(UPSARS II評分)無明顯相關(guān)性。ROC曲線分析顯示血清YKL-40濃度在多系統(tǒng)萎縮患者與健康人之間無明確診斷價值(A=0.264)。病例組血清CD40濃度為120.39(39.47)pg/ml,對照組為116.12(35.85)pg/ml,兩組間血清CD40濃度差異沒有統(tǒng)計學(xué)意義(P=0.871)。結(jié)論:1.多系統(tǒng)萎縮包括MSA-P型和MSA-C型兩種亞型,分別占47%和53%,平均發(fā)病年齡為59.43±10.04歲,無明顯性別差異;2.血清中YKL-40濃度與健康人的年齡、性別無明顯相關(guān)性,與多系統(tǒng)萎縮的臨床亞型(MSA-P型與MSA-C型)、發(fā)病年齡、病程和疾病嚴(yán)重情況無明顯相關(guān)性;3.多系統(tǒng)萎縮患者血清YKL-40濃度較健康人顯著降低,可能與NF-κB信號轉(zhuǎn)導(dǎo)通路功能變化,調(diào)控YKL-40表達(dá)發(fā)生改變相關(guān);4.血清YKL-40濃度不能用于多系統(tǒng)萎縮患者與健康人之間的鑒別診斷;5.多系統(tǒng)萎縮患者血清中CD40濃度較健康人無明顯變化。
[Abstract]:Objective: Multiple system atrophy (MSA) is a neurodegenerative disease with unknown etiology, with Parkinson like symptoms, ataxia and autonomic nervous dysfunction. The pathological changes of this disease are extensive neuron loss and glial cell proliferation. A large number of oligodendrocyte inclusion containing silvery fibrous filament The formation of Glial cytoplasmic inclusions (GCIs) is a pathological marker. The inclusion bodies of oligodendrocytes mainly contain false folds, highly phosphorylated alpha synuclein (alpha -synuclein, alpha -syn). Alpha synuclein is associated with the degeneration of neuron and the process of disease, and its abnormal expression is regulated by the signal transduction system of NF- kappa B. However, there is a complex and close relationship between the function of the NF- kappa B reaction system and the expression of cytokine YKL-40 (Chitinase3-Like-1, CHI3L1) and CD40. This study mainly discusses the differences between YKL-40, CD40 and healthy people in the sera of patients with multiple system atrophy, as well as the age, course of disease and the severity of disease in patients with multiple system atrophy. In order to further explore the pathogenesis of multiple system atrophy, the correlation is to seek the biomarkers of the diagnostic value of multiple system atrophy. Methods: the case group in this study was 30 cases of multiple system atrophy (14 cases, 14 MSA-C, 16 cases), which were in accordance with the revised Gilman diagnostic criteria of 2008 (type MSA-P, 16 cases), all were Dalian, 2013-2014 years. In the control group, 30 cases of "healthy people" of.30 MSA patients with the exception of neurologic diseases, tumor diseases, inflammatory diseases and infectious diseases were all accepted by the unified multiple system atrophy assessment scale (Unified Multiple System Atrophy Rating Scale, UMSARS) part II. The serum concentration of YKL-40 and CD40 in the case group and the control group was detected by the enzyme linked immunosorbent assay (Enzyme linked Immunosorbent Assay, ELISA). The difference between the serum YKL-40, CD40 concentration and the "healthy person" in the patients with multiple system atrophy was statistically analyzed, and the incidence of multiple system atrophy in patients with multiple system atrophy was analyzed. Correlation between age, course of disease and UMSARS II score. Statistical analysis was carried out by SPSS13.0 statistical package, and significant level of alpha was designed as a result of 0.05.. There were 30 cases of multiple system atrophy in case group, including 14 cases of MSA-P and 16 cases of MSA-C type, accounting for 47% and 53% respectively, with an average age of 59.43 + 10.04 years. The concentration of YKL-40 in the middle of the Qing Dynasty was 38.32 (11.74) ng/ml and the control group was 44.74 + 9.95 ng/ml. The difference of serum YKL-40 concentration between the two groups was statistically significant (P=0.002). The serum YKL-40 concentration in the case group was significantly lower than that of the control group. The serum YKL-40 level was not significantly related to the control age and the sex of the control group, and the clinical subtype of the multiple system atrophy in the case group (MSA-P and M). There was no significant correlation between the onset age, the course of disease and the severity of the disease (UPSARS II score). The.ROC curve analysis showed that the serum YKL-40 concentration had no definite diagnostic value between the patients with multiple system atrophy and the healthy person (A=0.264). The serum CD40 concentration was 120.39 (39.47) pg/ml, the control group was 116.12 (35.85) pg/ml, and the serum CD40 concentration was between the two groups. The difference was not statistically significant (P=0.871). Conclusion: 1. system atrophy includes two subtypes of type MSA-P and MSA-C, accounting for 47% and 53% respectively, the average age of onset is 59.43 + 10.04 years, and there is no significant gender difference. 2. serum YKL-40 concentration is associated with the age of healthy people, sex unmarked correlation, and the clinical subtype of multiple system atrophy (MSA-P and MSA-). C type), there was no significant correlation between the onset age, the course of disease and the serious condition of the disease. 3. the serum YKL-40 concentration in the patients with multiple system atrophy was significantly lower than that of the healthy people. It may be related to the changes in the function of the NF- kappa B signal transduction pathway and the regulation of the change of YKL-40 expression; 4. serum YKL-40 concentration could not be used for the differential diagnosis between the patients with multiple system atrophy and the healthy people. The serum concentration of CD40 in 5. patients with multiple system atrophy did not change significantly.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R741

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