血清中YKL-40、CD40与多系统萎缩的相关性研究

发布时间：2018-06-27 13:17

本文选题：多系统萎缩 + NF-κB　；参考：《大连医科大学》2015年硕士论文

【摘要】：目的:多系统萎缩(Multiple system atrophy,MSA)是一种病因不明,以帕金森样症状、共济失调和自主神经功能紊乱为主的神经系统变性疾病。本病的病理改变为广泛的神经元缺失及神经胶质细胞增生。大量含嗜银性纤维丝的少突胶质细胞包涵体(Glial cytoplasmic inclusions,GCIs)形成是其病理学标记。少突胶质细胞包涵体主要包含错误折叠、高度磷酸化α-突触核蛋白(α-synuclein,α-syn)。α-突触核蛋白与神经元退行性改变以及疾病进程密切相关,其异常表达受NF-κB信号转导体系的调控。然而,NF-κB反应体系的功能与细胞因子YKL-40(Chitinase3-Like-1,CHI3L1)和CD40的表达之间存在着复杂而密切的联系。本研究主要探讨多系统萎缩患者血清中YKL-40、CD40与健康人之间差异,以及其与多系统萎缩患者发病年龄、病程、疾病严重程度的相关性,为进一步探求多系统萎缩的发病机制奠定基础,以期寻求具有多系统萎缩诊断价值的生物标记物。方法:本研究中病例组为符合2008年修订的Gilman诊断标准的多系统萎缩患者共30例(MSA-P型14例,MSA-C型16例),均为2013-2014年间大连医科大学附属第一医院神经内科的住院患者。对照组为除外明确神经系统疾病、肿瘤性疾病、炎症性疾病和传染性疾病的“健康人”30例。30例MSA患者均接受了统一多系统萎缩评定量表(Unified Multiple System Atrophy Rating Scale,UMSARS)第II部分评估。利用酶联免疫吸附试验(Enzyme linked Immunosorbent Assay,ELISA)双抗体夹心法检测病例组和对照组血清中YKL-40与CD40浓度。多系统萎缩患者血清YKL-40、CD40浓度与“健康人”之间的差异进行了统计学分析,并分析了其与多系统萎缩患者发病年龄、病程和UMSARS II评分之间的相关性。统计学分析采用SPSS13.0统计软件包处理,设计显著水平α为0.05。结果:病例组多系统萎缩患者共30例,其中MSA-P型14例,MSA-C型16例,分别占47%和53%,无明显性别差异,平均发病年龄为59.43±10.04岁。病例组血清中YKL-40浓度为38.32(11.74)ng/ml,对照组为44.74±9.95 ng/ml,两组间血清YKL-40浓度差异具有统计学意义(P=0.002),病例组血清YKL-40浓度明显低于对照组。血清YKL-40水平与对照组年龄、性别无明显相关性,与病例组多系统萎缩的临床亚型(MSA-P型与MSA-C型)、发病年龄、病程和疾病严重程度(UPSARS II评分)无明显相关性。ROC曲线分析显示血清YKL-40浓度在多系统萎缩患者与健康人之间无明确诊断价值(A=0.264)。病例组血清CD40浓度为120.39(39.47)pg/ml,对照组为116.12(35.85)pg/ml,两组间血清CD40浓度差异没有统计学意义(P=0.871)。结论:1.多系统萎缩包括MSA-P型和MSA-C型两种亚型,分别占47%和53%,平均发病年龄为59.43±10.04岁,无明显性别差异;2.血清中YKL-40浓度与健康人的年龄、性别无明显相关性,与多系统萎缩的临床亚型(MSA-P型与MSA-C型)、发病年龄、病程和疾病严重情况无明显相关性;3.多系统萎缩患者血清YKL-40浓度较健康人显著降低,可能与NF-κB信号转导通路功能变化,调控YKL-40表达发生改变相关;4.血清YKL-40浓度不能用于多系统萎缩患者与健康人之间的鉴别诊断;5.多系统萎缩患者血清中CD40浓度较健康人无明显变化。
[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.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R741

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