血清sRAGE水平与系统性红斑狼疮疾病活动度相关性的研究
发布时间：2018-10-22 19:49
【摘要】：引言系统性红斑狼疮(SLE)是一种累及多器官、多系统的自身免疫性疾病,以产生针对自身核抗原如DNA、RNA及其他细胞核成分的多种自身抗体为特征,是自身免疫性疾病的原型。该病好发于育龄期女性,男女患病比例约为1:9。在SLE患者的病程中几乎所有的器官(如皮肤黏膜、关节、肾脏、大脑、心血管及胃肠道等)均能累及,且缓解与复发交替的特点使得几乎所有的狼疮患者都需要接受终生抗狼疮治疗,对社会及患者本人带来了巨大的经济负担及精神心理压力,具有严重的危害性。该病的发病机制十分复杂,至今尚未完全阐明。近年来各研究组从未停止对其发病机制的研究:研究表明大量分子或细胞因子参与到该病的发病过程中,且在该病的发病机制中发挥重要作用。可溶性晚期糖基化终产物受体(s RAGE)就是新近发现的可能在SLE发病机制中发挥重要作用的一种蛋白质分子,它是细胞表面晚期糖基化终产物受体(RAGE)的可溶形式,可由RAGE的信使RNA经过选择性剪接[1-3]或经基质金属蛋白酶MMP-9或ADAM10裂解产生[4,5],属于免疫球蛋白超家族成员之一[6]。s RAGE是一种多配体受体,能够与多种内源性配体结合,如晚期糖基化终产物(AGEs)、S100/钙粒蛋白家族、高迁移率族蛋白-1(HMGB1)、β淀粉样蛋白、β2-整合素Mac-1等[7-10]。因其仅含有与RAGE相同的细胞外配体结合区域,缺乏跨膜区域和胞质尾区,因此s RAGE只具有配体结合功能,而不具有细胞内信号传导功能。由于这一特性,s RAGE被称为“诱饵”受体,多数研究表明它能够竞争性的拮抗RAGE的功能,在配体到达细胞表面与RAGE结合之前提前与其结合,阻断NF-κB的核转移以及下游效应因子如肿瘤坏死因子α(TNF-α)、白介素6(IL-6)等细胞因子的活化,抑制细胞内炎症的级联反应,从而保护易感细胞免于因受这些受体的活化而带来的潜在毒害效应[6]。然而,关于s RAGE的特性及其调节炎症反应的具体作用机制尚不清楚,仍需进一步阐明。目前关于s RAGE在SLE发病机制中的研究已成为各狼疮研究小组的热点,人们试图探讨s RAGE是否能够成为评价狼疮疾病活动度的新的生物标志物。尽管如此,关于血清s RAGE浓度水平与SLE疾病活动度之间的相关研究仍旧是有限的,且不能形成统一认识,仍需要大量多中心随机双盲对照研究进行证实。我们的研究纳入大量样本,旨在发现血清s RAGE浓度水平与SLE疾病活动度及其相关实验室检查指标之间的相关性,评价其是否能够成为一种评估SLE疾病活动度的新的生物标志物,从而为进一步制定个体化治疗方案提供一定的依据。目的探讨血清s RAGE浓度水平是否与SLE疾病活动度之间存在相关性。方法1.收集2013年6月至2014年6月期间就诊于郑州大学第一附属医院风湿免疫科和肾病科的SLE患者共104名,收集所有SLE患者的一般情况、临床特征资料以及实验室检查结果,并采集所有患者的血标本,离心后取上清置于-80℃冰箱中保存。2.应用酶联免疫吸附法(ELISA)检测血清中s RAGE的浓度水平。按照SLEDAI评分将SLE患者分为两组:SLEDIA评分0-4分为非活动性SLE患者组;SLEDIA评分≥5分为活动性SLE患者组,并分析血清s RAGE浓度水平在各组之间的差异以及血清s RAGE浓度水平与临床各参数以及狼疮疾病活动度之间的相关性;3.使用统计分析软件SPSS 17.0(Chicago,Illinois,USA)进行统计学分析,定量资料使用均数±标准差(x±s)进行表示,定性资料使用百分比(%)进行表示。使用非参数检验Mann-Whitney U检验进行两组间定量资料的比较,Spearman秩相关分析用来分析评价某一个参数与血清s RAGE浓度水平之间的相关性。P0.05被认为具有统计学意义。结果1.血清s RAGE浓度水平在活动性SLE患者组中比在非活动性SLE患者组中显著增高,差异具有统计学意义(Z=-2.673,p=0.008)。2.血清s RAGE浓度水平与临床各参数之间的相关性分析:血清s RAGE浓度水平与抗ds-DNA抗体滴度(CI=0.268,p=0.008)、24小时尿总蛋白定量(CI=0.387,p=0.001)以及SLEDAI评分(CI=0.373,p=0.000)之间具有正相关关系;与血白细胞计数(CI=-0.230,p=0.020)、补体C3(CI=-0.371,p=0.000)及补体C4(CI=-0.280,p=0.000)之间具有负相关关系;结论血清s RAGE浓度水平与SLE疾病活动度之间呈正相关,可能成为评价SLE患者疾病活动性的新的生物标志物。
[Abstract]:Foreword systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and multiple systems to produce a variety of autoantibodies against their nuclear antigens, such as DNA, RNA and other nuclear components, and is a prototype of autoimmune diseases. The morbidity of the disease is about 1: 9. Almost all organs (such as skin mucosa, joint, kidney, brain, cardiovascular and gastrointestinal tract, etc.) can be involved in the course of SLE patients, with the characteristics of alternating response and recurrence, so that almost all patients with lupus need to receive lifelong anti-lupus therapy, It brings huge economic burden and mental stress to society and patient, and has serious harm. The pathogenesis of the disease is very complicated and has not yet been fully elucidated. In recent years, research groups have never stopped studying the pathogenesis of the disease: research indicates that a large number of molecules or cytokines are involved in the pathogenesis of the disease and play an important role in the pathogenesis of the disease. Soluble late glycation end product receptor (s RAGE) is a newly discovered protein molecule which may play an important role in the pathogenesis of SLE, which is a soluble form of advanced glycation end product receptor (RAGE) in cell surface.[4,5] can be produced by selective splicing of RAGE messenger RNA[1-3] or by matrix metalloproteinase-9 or ADAM10 cleavage[4, 5], belonging to one of the immunoglobulin members[6]. s RAGE is a multi-ligand receptor capable of binding to a variety of endogenous ligands, such as advanced glycation end products (AGEs), S100/ calcium particle protein family, high mobility group protein-1 (HMGB1), waxy starch-like protein, SO42-whole-element Mac-1, etc.[7-10]. Because they contain only the same extracellular ligand binding region as RAGE, there is a lack of transmembrane regions and cytoplasmic tail regions, so s RAGE only has ligand binding function without intracellular signal transduction. As a result of this feature, s RAGE is referred to as" bait "Most studies have shown that it can competitively antagonize RAGE's function, bind to it in advance before the ligand reaches the cell surface to bind RAGE, block the nuclear transfer of NF-Sepharose B and the activation of downstream effector factors such as tumor necrosis factor (TNF-gamma), interleukin 6 (IL-6) and other cytokines, Cascade responses that inhibit inflammation in cells, thereby protecting sensitive cells from potentially toxic effects due to activation of these receptors[6]. However, the specific mechanism of action regarding s RAGE and its regulatory inflammatory response is not yet clear and still need to be further elucidated. At present, the research on s RAGE in the pathogenesis of SLE has become the focus of the lupus research team, and people are trying to explore whether the s RAGE can be a new biomarker for evaluating the activity of lupus disease. Nevertheless, the study on serum s RAGE concentration level and SLE disease activity remains limited and does not form a unified understanding and requires a large number of multicenter randomized double-blind control studies. Our study included a large number of samples to detect the correlation between serum s RAGE concentration level and SLE disease activity and its associated laboratory test indices, and evaluate whether it could be a new biomarker for evaluating the activity of SLE disease, so as to provide a certain basis for further developing an individualized treatment plan. Objective To investigate the correlation between serum s RAGE concentration level and activity of SLE disease. Method 1. Collect 104 SLE patients who visited the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2014 in the First Affiliated Hospital of Zhengzhou University, collected total of 104 SLE patients, clinical features and laboratory results, and collected blood samples from all patients. taking supernatant after centrifugation and placing the supernatant in a refrigerator at -80 DEG C for storage. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration level of s RAGE in serum. SLE patients were divided into two groups according to SLEDAI score: SLEDIA score 0-4 was divided into inactive SLE patients group; SLEDIA score group 5 was divided into active SLE patients group. The correlation between serum s RAGE concentration level and serum s RAGE concentration level and clinical parameters as well as the activity of lupus disease was analyzed. Statistical analysis was performed using SPSS 17. 0 (Chicago, Illinois, USA) using the statistical analysis software, and the quantitative data were expressed using standard deviation (x/ s), and the qualitative data were expressed as a percentage (%). The comparison between the two sets of quantitative data was performed using a non-exponential test Mann-Whitney U test, and Spearman rank correlation analysis was used to analyze the correlation between the evaluation of a certain parameter and the serum s RAGE concentration level. P0. 05 was considered to be statistically significant. Result 1. Serum s RAGE concentration was significantly higher in active SLE patients than in inactive SLE patients (Z =-2.673, p = 0.0008). Correlation analysis between serum s RAGE concentration level and clinical parameters: serum s RAGE concentration level was positively correlated with anti ds-DNA antibody drop (CI = 0.268, p = 0.0008), 24-hour urinary total protein ration (CI = 0.387, p = 0.0001) and SLEDAI score (CI = 0.373, p = 0. 000); and blood white blood cell count (CI =-0.230, p = 0.020), There was a negative correlation between complement C3 (CI =-0.371, p = 0. 000) and complement C4 (CI =-0.280, p = 0. 000). Conclusion The level of serum s RAGE is positively correlated with the activity of SLE, and it may be a new biomarker to evaluate the disease activity of SLE patients.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.241
[Abstract]:Foreword systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and multiple systems to produce a variety of autoantibodies against their nuclear antigens, such as DNA, RNA and other nuclear components, and is a prototype of autoimmune diseases. The morbidity of the disease is about 1: 9. Almost all organs (such as skin mucosa, joint, kidney, brain, cardiovascular and gastrointestinal tract, etc.) can be involved in the course of SLE patients, with the characteristics of alternating response and recurrence, so that almost all patients with lupus need to receive lifelong anti-lupus therapy, It brings huge economic burden and mental stress to society and patient, and has serious harm. The pathogenesis of the disease is very complicated and has not yet been fully elucidated. In recent years, research groups have never stopped studying the pathogenesis of the disease: research indicates that a large number of molecules or cytokines are involved in the pathogenesis of the disease and play an important role in the pathogenesis of the disease. Soluble late glycation end product receptor (s RAGE) is a newly discovered protein molecule which may play an important role in the pathogenesis of SLE, which is a soluble form of advanced glycation end product receptor (RAGE) in cell surface.[4,5] can be produced by selective splicing of RAGE messenger RNA[1-3] or by matrix metalloproteinase-9 or ADAM10 cleavage[4, 5], belonging to one of the immunoglobulin members[6]. s RAGE is a multi-ligand receptor capable of binding to a variety of endogenous ligands, such as advanced glycation end products (AGEs), S100/ calcium particle protein family, high mobility group protein-1 (HMGB1), waxy starch-like protein, SO42-whole-element Mac-1, etc.[7-10]. Because they contain only the same extracellular ligand binding region as RAGE, there is a lack of transmembrane regions and cytoplasmic tail regions, so s RAGE only has ligand binding function without intracellular signal transduction. As a result of this feature, s RAGE is referred to as" bait "Most studies have shown that it can competitively antagonize RAGE's function, bind to it in advance before the ligand reaches the cell surface to bind RAGE, block the nuclear transfer of NF-Sepharose B and the activation of downstream effector factors such as tumor necrosis factor (TNF-gamma), interleukin 6 (IL-6) and other cytokines, Cascade responses that inhibit inflammation in cells, thereby protecting sensitive cells from potentially toxic effects due to activation of these receptors[6]. However, the specific mechanism of action regarding s RAGE and its regulatory inflammatory response is not yet clear and still need to be further elucidated. At present, the research on s RAGE in the pathogenesis of SLE has become the focus of the lupus research team, and people are trying to explore whether the s RAGE can be a new biomarker for evaluating the activity of lupus disease. Nevertheless, the study on serum s RAGE concentration level and SLE disease activity remains limited and does not form a unified understanding and requires a large number of multicenter randomized double-blind control studies. Our study included a large number of samples to detect the correlation between serum s RAGE concentration level and SLE disease activity and its associated laboratory test indices, and evaluate whether it could be a new biomarker for evaluating the activity of SLE disease, so as to provide a certain basis for further developing an individualized treatment plan. Objective To investigate the correlation between serum s RAGE concentration level and activity of SLE disease. Method 1. Collect 104 SLE patients who visited the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2014 in the First Affiliated Hospital of Zhengzhou University, collected total of 104 SLE patients, clinical features and laboratory results, and collected blood samples from all patients. taking supernatant after centrifugation and placing the supernatant in a refrigerator at -80 DEG C for storage. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration level of s RAGE in serum. SLE patients were divided into two groups according to SLEDAI score: SLEDIA score 0-4 was divided into inactive SLE patients group; SLEDIA score group 5 was divided into active SLE patients group. The correlation between serum s RAGE concentration level and serum s RAGE concentration level and clinical parameters as well as the activity of lupus disease was analyzed. Statistical analysis was performed using SPSS 17. 0 (Chicago, Illinois, USA) using the statistical analysis software, and the quantitative data were expressed using standard deviation (x/ s), and the qualitative data were expressed as a percentage (%). The comparison between the two sets of quantitative data was performed using a non-exponential test Mann-Whitney U test, and Spearman rank correlation analysis was used to analyze the correlation between the evaluation of a certain parameter and the serum s RAGE concentration level. P0. 05 was considered to be statistically significant. Result 1. Serum s RAGE concentration was significantly higher in active SLE patients than in inactive SLE patients (Z =-2.673, p = 0.0008). Correlation analysis between serum s RAGE concentration level and clinical parameters: serum s RAGE concentration level was positively correlated with anti ds-DNA antibody drop (CI = 0.268, p = 0.0008), 24-hour urinary total protein ration (CI = 0.387, p = 0.0001) and SLEDAI score (CI = 0.373, p = 0. 000); and blood white blood cell count (CI =-0.230, p = 0.020), There was a negative correlation between complement C3 (CI =-0.371, p = 0. 000) and complement C4 (CI =-0.280, p = 0. 000). Conclusion The level of serum s RAGE is positively correlated with the activity of SLE, and it may be a new biomarker to evaluate the disease activity of SLE patients.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.241
【相似文献】
相关期刊论文 前5条
1 俞乃昌,周晓华,王红;定量检测血浆DNA评估SLE的疾病活动度[J];山西医药杂志;1998年02期
2 周洁;袁洁璐;王正廷;俞骁s，
本文编号：2288141
本文链接：https://www.wllwen.com/yixuelunwen/nfm/2288141.html
最近更新
教材专著
