系统性红斑狼疮论文：系统性红斑狼疮 青蒿琥酯 干扰素诱导基因 血管内皮细胞生长因子 巨噬细胞移动抑制因子 动脉粥样硬化
系统性红斑狼疮论文：系统性红斑狼疮 青蒿琥酯 干扰素诱导基因 血管内皮细胞生长因子 巨噬细胞移动抑制因子 动脉粥样硬化【中文摘要】探讨系统性红斑狼疮(SLE)患者中动脉粥样硬化相关因子的表达与疾病活动性或传统风险因素的关联性；通过体外研究观察青蒿琥酯(ART)对这些因子的调控作用并初步探讨其可能的机制,为狼疮早发动脉粥样硬化的防治提供一定的理论和实验依据。方法1、搜集35例SLE患者的临床资料,分别计算出疾病活动指数(SLEDAI)、10年内发生严重心血管事件危险率,检测相应患者血浆中血管内皮细胞生长因子(VEGF)及巨噬细胞移动抑制因子(MIF)水平,并根据干扰素(IFN)诱导基因表达水平计算干扰素指数,根据危险率或SLEDAI上下把SLE组分为两组,用t检验分别检测两组间的VEGF、MIF、干扰素指数；另分析10年内发生严重心血管事件危险率与SLEDAI的相关性。2、收集7例SLE患者的外周血,别离外周血单个核细胞(PBMC)。每个患者的PBMC分为两组：ART组(5mol/LART处理)和对照组,12小时后以实时荧光定量逆转录聚合酶链反响(Q-PCR)法检测细胞中型IFN诱导基因LY6E、ISG15mRNA的表达水平,酶联免疫吸附试验(ELISA)法检测培养上清液中VEGF及MIF水平。3、用不同剂量(0,5、20mol/L)的ART处理有/无IFN-1b刺激的人脐静脉内皮细胞(HUVEC)6.12或24小时,以Q-PCR检测细胞中LY6E、ISG15mRNA的表达水平,ELISA检测培养上清液VEGF及MIF水平。以地塞米松(DEX)为阳性对照组。结果1、SLEDAI高分组较低分组MIF水平显著升高(p=0.002),VEGF水平显著降低(p=0.02),干扰素指数显著升高(p=0.028)；SLE患者发生严重心血管事件高风险组与低风险组比其MIF水平较高但无统计学意义,VEGF及干扰素指数无明显变化；SLE患者10年内发生心血管事件危险率与疾病活动指标SLEDAI评分具有一定相关性(r=0.365,p0.05)。结论1、狼疮患者动脉粥样硬化相关因子与疾病本身及其活动关系较密切,而与传统的动脉粥样硬化危险因素无关,提示狼疮疾病活动在动脉粥样硬化发生过程中起主导作用。2、青蒿琥酯可以抑制狼疮患者PBMC中VEGF、MIF的分泌,并下调干扰素诱导基因的表达。3、青蒿琥酯可以下调HUVEC干扰素诱导基因的表达,从而降低VEGF和MIF的分泌,通过IFN刺激试验进一步证实青蒿琥酯对动脉粥样硬化因子的调控作用。【英文摘要】1) To find out the relationship between atherosclerosis-related factors (MIF and VEGF) and disease activity as well as tranditional atherosclerotic risk factors in patients with systemic lupus erythematosus (SLE).2) To investigate the effect of artesunate on the regulation of these factors and to elucidate its potential mechanisms.Methods1. Clinical data were obtained from 35 SLE patients, with their SLEDAI scores and estimated 10-year risks of developing Hard CHD (Myocardial Infarction and Coronary Death) calculated. Serum levels of VEGF and MIF were measured by ELISA and expressions of interferon inducible genes were detected by real-time PCR. Whether patients with SLEDAI score >7 or estimated 10-year risks0.01 had abnoraml level of VEGF, MIF and interferon score were tested. And analysis the correlation between 10-year CHD risk and SLEDAI.2. Peripheral blood mononuclear cells (PBMC) were collected from 7 SLE patients. Each PBMC sample was divided into two groups:1) 5mol/L ART treatment,2) control. After culturing for 12 hours, cells were harvested and total RNA was extracted and reverse transcribed into cDNA. Real-time PCR technique was used to determine the expressions of ISG15 and LY6E (two major IFN inducible genes) at transcription level. The levels of VEGF and MIF in supernatant were evaluated by ELISA.3. Human umbilical vein endothelial cells (HUVEC) were treated by ART at a dose of 5 or 20mol/L or treated by dexamethasone as a positive control after exposure to IFN-1b 6,12 or 24hours. Real-time PCR was used to determine the gene expressions of ISG15 and LY6E at transcription level, and the levels of VEGF and MIF in supernatant were evaluated by ELISA.Results1. Compared with patients having SLEDAI score0.05).Conclusions:1. Atherosclerosis related factors (MIF and VEGF) in SLE patients are related to the disease itself and its activities, but not thetraditional risk factors for atherosclerosis, suggesting that disease activity play a mojor role in the process of atherosclerosis in lupus.2. ART is able to inhibit the expression of interferon-inducible genes and decrease the secretion of VEGF and MIF in SLE patients.3. Artesunate can reduce the expression of interferon induced genes and correspondingly secretion of VEGF and MIFin HUVEC, confirming that artesunate may have therapeutic effect on the modulating of atherosclerosis related factors in SLE patients.【关键词】系统性红斑狼疮 青蒿琥酯 干扰素诱导基因 血管内皮细胞生长因子 巨噬细胞移动抑制因子 动脉粥样硬化【采买全文】 1.3.9.9.38.8.4.8 1.3.8.1.13.7.2.1 同时提供论文写作一对一辅导和论文发表效劳.保过包发. 【说明】本文仅为中国学术文献总库合作提供，无涉版权。作者如有异议请与总库或学校联系。 【英文关键词】Systemic lupus erythematosus Artesunate Interferon-inducible gene Vascular endothelial growth factor Macrophage migration inhibitory factor Atherosclerosis【目录】青蒿琥酯对狼疮患者动脉粥样硬化相关因子的影响摘要6-8Abstract8-9前言10-13第一局部 狼疮与动脉粥样硬化相关因子相关性研究13-20病例与方法13-16结果16-18讨论18-20第二局部 青蒿琥酯对SLE外周血单个核细胞VEGF、MIF、IFN诱导基因的影响20-32实验材料和方法20-28结果28-30讨论30-32第三局部 青蒿琥酯对人脐静脉内皮细胞VEGF、MIF及IFN诱导基因的影响32-41实验材料及方法32-35结果35-39讨论39-41结论41-42参考文献42-47附录47-55(一) 综述47-54参考文献51-54(二) 主要缩略词表54-55攻读硕士学位期间取得的学术成果55-56致谢56
