视神经脊髓炎患者体内抵抗素水平变化及意义的研究

发布时间：2018-05-14 12:25

本文选题：视神经脊髓炎 + 抵抗素　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的视神经脊髓炎(Neuromyelitis optica,NMO)是一种罕见的中枢神经系统(central nervous system,CNS)自身免疫性星形胶质细胞病,其发病是抗体及多种炎症细胞、因子等共同作用的结果。抵抗素是近年发现的在多种炎性疾病中发挥重要作用的脂肪细胞因子。本文旨在研究抵抗素在NMO中的作用。方法纳入急性期NMO患者及年龄性别相匹配的健康对照组(Healthy controls,HCs)各56例,同时纳入非炎症性神经系统疾病(non-inflammatory neurological disorders,ONNDs)患者12例作为疾病对照组。采集受试对象标本并记录人口学信息及临床资料,如体重指数(Body mass index,BMI)、血糖(Glucose,Glu)、总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、高密度脂蛋白(High density lipoprotein,HDL)、低密度脂蛋白(Low density lipoprotein,LDL)、超敏C反应蛋白(high sensitive C reactive protein,hs-CRP)、疾病首发年龄、病程、年复发率(annualized relapse rate,ARR)、脊髓受累节段数及扩展残疾状态量表(Expanded Disability Status Scale,EDSS)评分等。应用细胞荧光免疫染色法(Cell-based immunofluorescence assay,CBA)检测NMO患者血清中水通道蛋白4抗体(Aquaporin-4 antibody,AQP4-Ab)水平,同时应用酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测所有研究对象血清和CSF中抵抗素含量以及NMO患者予以大剂量激素冲击后血清抵抗素水平。分类资料采用χ2检验进行分析。正态分布计量资料采用学生t检验分析组间(NMO组、健康对照组、疾病对照组)差异;非正态分布计量资料采用Mann Whitney U检验进行分析;BMI、Glu、TC、TG、HDL、LDL等的作用通过作为协变量加入到分析模型中进行分析。配对t检验用于NMO组治疗前后亚组间差异的比较,Spearman相关检验用于统计标本resistin水平与患者临床特点间的相关性。P0.05视为差异具有统计学意义。结果1、NMO组中有44例患者AQP4-Ab为阳性,阳性率为78.6%;2、急性期NMO患者血清抵抗素水平较HCs明显升高(7.6±3.0 vs 4.1±1.4 ng/ml,p0.001),另外,血清hs-CRP水平在急性期NMO患者中同样高于HCs(2.0±1.9vs 0.8±0.9mg/l,p=0.017);3、急性期NMO患者CSF中抵抗素水平较ONNDs组明显升高(0.25±0.23 vs 0.04±0.01 ng/ml,p=0.001);4、NMO患者血清及CSF中抵抗素水平与hs-CRP呈正相关性,且差异具有统计学意义(r=0.303,p=0.023;r=0.622,p=0.003);5、NMO患者BMI及血清TG水平与HCs无明显差异(p0.05),而Glu、TC、LDL和HDL与HCs间差异具有统计学意义(5.3±0.8 vs 4.5±0.5mmol/l,p0.001;5.0±1.1 vs 4.2±0.5 mmol/l,p0.001;3.1±0.9 vs 2.3±0.6 mmol/l,p0.001;1.3±0.4 vs 1.5±0.4 mmol/l,p=0.025),但协方差分析结果无显著性差异(p0.05);6、急性期NMO患者血清抵抗素水平与ARR存在正相关性(r=0.354,p=0.007),但与疾病首发年龄、病程、脊髓受累节段数、EDSS评分以及AQP4-Ab水平无明显相关性;7、16例应用大剂量激素冲击的NMO患者在治疗后血清抵抗素水平较治疗前显著减低(8.6±3.3 vs 4.7±1.5 ng/ml,p0.001)。结论1.抵抗素可能参与了NMO的发生和发展过程,并且在疾病中起到促进炎症反应的作用;2.NMO患者CSF中抵抗素明显升高,提示其可通过破坏的血脑屏障进入CNS发挥炎性作用;3.抵抗素炎性作用的发挥可能与hs-CRP存在一定相关性;4.血清抵抗素水平高低对于疾病的复发可能具有一定的预测作用,但与疾病的严重程度尚未发现存在明显相关性;5.抵抗素在疾病恢复期降低,提示其可能成为评价疾病进程的指标之一,并可能成为NMO治疗的潜在靶点。
[Abstract]:Objective Neuromyelitis optica (NMO) is a rare autoimmune astrocytic disease of the central nervous system (central nervous system, CNS), which is the result of the joint action of antibodies and a variety of inflammatory cells and factors. Resistin is found in recent years to play an important role in a variety of inflammatory diseases. The purpose of this study was to study the role of resistin in NMO. Methods 56 cases of acute NMO patients and 56 cases of matched age and sex healthy control group (Healthy controls, HCs) were included, and 12 cases of non inflammatory nervous system disease (non-inflammatory neurological disorders, ONNDs) were included as the disease control group. Sample and record demographic information and clinical data, such as body mass index (Body mass index, BMI), blood glucose (Glucose, Glu), total cholesterol (Total cholesterol, TC), triglycerides (Triglyceride, TG), high-density lipoprotein, low density lipoprotein (LDL), hypersensitive reactive protein Sitive C reactive protein, hs-CRP), the onset age of the disease, the course of disease, the annual recurrence rate (annualized relapse rate, ARR), the number of segmental spinal cord involvement and the scale of the extended disability state (Expanded Disability Status). The level of Aquaporin-4 antibody (AQP4-Ab) antibody (antibody, AQP4-Ab) and the serum and CSF levels of resistin in all the subjects and the level of resistin in all the subjects were detected by the enzyme linked immunosorbent assay (Enzyme linked immunosorbent assay, ELISA). The classification data were analyzed by chi square test. Normal distribution measurement data were used by students t test and Analysis Group (group NMO, health control group and disease control group); non normal distribution measurement data were analyzed by Mann Whitney U test; BMI, Glu, TC, TG, HDL, LDL, etc. were added to the analysis model as co variables. Comparison of the differences between subgroups, Spearman correlation test used the statistical significance of the correlation between the resistin level of statistical specimens and the clinical characteristics of the patients. Results 1, 44 cases in group NMO were AQP4-Ab positive, the positive rate was 78.6%; 2, the level of serum resistin in patients with acute phase NMO was significantly higher than that of HCs (7.6 + 3 vs 4.1 + 1.4. Ng/ml, p0.001), in addition, the level of serum hs-CRP in acute NMO patients was also higher than HCs (2 + 1.9vs 0.8 + 0.9mg/l, p=0.017); 3, the level of resistin in CSF in acute stage NMO was significantly higher than that in ONNDs group (0.25 + 0.23 vs 0.04 + 0.01), and 4. Statistical significance (r=0.303, p=0.023; r=0.622, p=0.003); 5, there was no significant difference between BMI and serum TG in NMO patients and HCs (P0.05), while Glu, TC, LDL and p=0.003 were statistically significant (5.3 + 0.8, 5 + 1.1, 4.2 + 0.5); 3.1 + 0.9 2.3 + 0.6 0.025) but there was no significant difference in covariance analysis (P0.05); 6, there was a positive correlation between serum resistin level and ARR in acute NMO patients (r=0.354, p=0.007), but there was no significant correlation with the onset age, the course of the disease, the number of spinal cord involvement, the EDSS score, and the level of AQP4-Ab; 7,16 cases were treated with large dose of hormone in the treatment of the patients. The level of serum resistin was significantly lower than that before the treatment (8.6 + 3.3 vs 4.7 + 1.5 ng/ml, p0.001). Conclusion 1. resistin may be involved in the development and development of NMO, and play a role in promoting the inflammatory reaction in the disease. The 2.NMO patients' resistin in CSF is obviously elevated, suggesting that it can enter CNS through the damaged blood brain barrier to play the inflammatory action. Use; 3. the inflammatory effect of 3. resistin may have a certain correlation with the presence of hs-CRP; 4. the level of serum resistin may have a certain predictive effect on the recurrence of the disease, but there is no obvious correlation with the severity of the disease; 5. resistin is reduced in the recovery period of the disease, suggesting that it may be the index of the evaluation of the disease process. One of the targets, and may be a potential target for NMO treatment.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R744.52

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