【作者】 杨磊；

【导师】 周嘉强；

【作者基本信息】 浙江大学 ， 内科学， 2013， 硕士

【摘要】 目的痛风是一种症状呈发作性的常见的晶体性关节炎。以IL-1为主线的一系列炎症因子在其发病中的重要作用已为众多研究所证实,但是不依赖IL-1的炎症因子在痛风中的变化规律有待阐明。本研究通过检测痛风急性发作患者血清趋化因子CC基序配体2(CCL2)和IL-10的浓度分析其潜在的变化规律及其相关因素。方法通过回顾性病例对照研究,收集男性痛风急性发作患者的临床一般资料：年龄、病程、本次发病时间、体重指数；生化指标：血尿酸、血尿素氮、血肌酐、血总胆固醇、血甘油三酯、血低密度脂蛋白、血高密度脂蛋白、血γ谷氨酰转肽酶、血碱性磷酸酶、血谷丙转氨酶、血谷草转氨酶；急性炎症反应物：血沉、C反应蛋白。ELISA法检测外周血CCL2和IL-10浓度。结果入选304例患者的血尿酸水平为7.4±2.6mg/dL,水平正常者为45.1%。按发作时间分为三组,<3d组血尿酸为7.5±2.5mg/dL,3-5d组为7.2±2.6mg/dL,>5d组为7.1±2.3mg/dL;三组血尿酸的正常者比例分别为46.0%、48.1%、46.2%,差异无统计学意义。血尿酸正常者和增高者的C反应蛋白水平分别为73.5±63.7和32.8±54.5mg/L,血沉分别为49.2±37.1和30.4±26.2mm/hr,两者差异均具有统计学意义(P<0.001)。血尿酸水平与血沉不相关,而与C反应蛋白呈负相关(P<0.01)。血尿酸正常者和增高者的血清CCL2浓度分别为995.8±644.2pg/mL和545.4±402.8pg/mL,差异具有显著统计学意义(P<0.001)。而按发作时间分组<3d者为689.2±535.0pg/mL,3-5d者为885.8±649.8pg/mL,>5d者为758.9±461.4pg/mL,差异无统计学意义。血尿酸正常者和增高者的血清IL-10浓度分别为75.6±41.6pg/mL和79.0±42.9pg/mL,两者差异无统计学意义。而按发作时间分组<3d者为64.1±33.8pg/mL,3-5d者为96.3±32.4pg/mL,>5d者为169.5±44.9pg/mL,三组差异具有显著统计学意义(P＜0.001),＞5d者和3-5d者均显著高于＜3d者(P＜0.001),而＞5d者与3-5d者相比,前者更高(P＜0.001)。相关性分析发现血清CCL2浓度与本次发作时间、Y谷氨酰胺转肽酶、碱性磷酸酶、血沉、C反应蛋白呈正相关(P＜0.05),而与血尿酸、血肌酐水平呈负相关(P＜0.05)；血清IL-10水平与本次发作时间、血沉、C反应蛋白呈正相关(P＜0.05)。结论在痛风急性发作时,血尿酸水平的高低并非疾病诊断的唯一标准,其水平与C反应蛋白密切相关。血清CCL2水平在血尿酸水平更高的痛风急性发作患者中更低,且与碱性磷酸酶、Y谷氨酰转肽酶、急性炎症反应物水平和血肾功能相关。血清IL-10水平随发作时间的延长而显著增高,很可能参与了痛风急性发作的炎症缓解过程。更多还原

【Abstract】 ObjectiveGout is a common crystal arthritis, and has episodes of acute attacks. A series of pro-inflammatory cytokines like IL-1, as an axis, were identified the important effect in the pathological process with gout by many studies. Therefore, the role of some mediators, not dependence on IL-1, was not clarified in gout. In this study, we want to explore the change of serum levels of CCL2and IL-10in patients with acute gouty arthritis and to analyze the effects of the potential associated factors on this status.MethodsThough this retrospective case controlled study, the demography data of male patients with gout acute flare were collected, including age, disease duration, time during the attack of gout and body index. Meanwhile, some clinical biochemistry parameters were determined, such as alanine aminotransferase, alanine aminotransferase, alkaline phosphatase, y-glutamyl-transpeptidase, cholesterol, triglyceride, low density lipoprotein, high density lipoprotein, blood urea nitrogen, serum creatinine, and also involved in acute inflammatory reactants:C reactive protein and ESR.The serum levels of CCL2and IL-10were determined by ELISA assay from R&D systems.ResultsThe mean of serum urate was7.4±2.6mg/dL in recruited304patients, and ratio of normal serum urate (cutoff value=7.0mg/dL) in them was45.1%. All patients were divided into three subgroups, according to the time during the attack of gout. There were not statistic significant among the serum urate of<3days (7.5±2.5mg/dL), of3-5days (7.2±2.6mg/dL), and of>5days (7.1±2.3mg/dL). The ratio of normal serum urate in three groups was46.0%(<3days),48.1%(3-5days), and46.2%(>5days), respectively (P>0.05). The level of CRP in normal serum urate group was higher than that in serum urate increase group,73.5±63.7mg/Lvs32.8±54.5mg/L (P<0.001). And the similar tendency was found to compare of ESR levels between two groups (normal or abnormal serum urate levels),49.2±37.1mm/hr vs30.4±26.2mm/hr (P<0.001). The level of serum urate was negatively related with CRP level (P<0.01) and no relationship with ESR by Spearman’s correlation analysis. Furthermore, the concentration of serum CCL2was995.8±644.2pg/mL in normal serum urate group and545.4±402.8pg/mL in serum urate increase group (P<0.001). But, there were insignificant in the concentration of serum CCL2among<3days (689.2±535.0pg/mL),3-5days (885.8±649.8pg/mL),and>5days (758.9±461.4pg/mL).The significance of serum IL-10concentration between normal serum urate (75.6±41.6pg/mL) and serum urate increase (79.0±42.9pg/mL) groups was not found. Though the elongation of time during the attack of gout, the concentration of serum IL-10, such as64.1±33.8pg/mL in<3days,96.3±32.4pg/mL in3-5days, and169.5±44.9pg/mL in>5days, increased observably (P<0.001).The Spearman correlation analysis indicated that the concentration of serum CCL2was positively related with time of the attack of gout, alkaline phosphatase, y-glutamyl-transpeptidase, ESR and CRP (P<0.05), and negatively related with serum urate and creatinine (P<0.05). Thus, the concentration of serum IL-10was positively related with time of the attack of gout, ESR and CRP (P<0.05).ConclusionSerum uric acid levels did not confirm or exclude gout during acute attacks, and was tightly related with CRP. The higher levels of serum uric acid were the lower concentration of serum CCL2in patients with an acute flare. There were significant associated with serum CCL2concentration and alkaline phosphatase, y-glutamyl-transpeptidase, acute inflammatory reactants, and creatinine. Serum IL-10levels increased significantly following the extension of the attack duration. The cytokine, IL-10, might be involve in the resolution process of acute inflammation in gout.更多还原