【作者】 李昕；

【导师】 郑曰忠；

【作者基本信息】 天津医科大学 ， 眼科学（专业学位）， 2013， 硕士

【摘要】 目的：1.观察葡萄膜炎患者的临床表现、并发症和治疗效果。2.比较并分析葡萄膜炎(前葡萄膜炎、中间葡萄膜炎和全葡萄膜炎)患者及健康对照组血清中肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)和白细胞介素17(IL-17)浓度、相互关系以及影响因素。3.探讨TNF-α、IL-10和IL-17在葡萄膜炎发病机制中的作用,探讨针对TNF-α、IL-10和IL-17的新治疗方法。方法：自2012年11月至2013年4月间,连续收集在天津市眼科医院门诊及住院治疗的各类葡萄膜炎患者65例,详细记录患者全身疾病史、眼病史以及临床诊治资料。65例患者中男35例,女30例；平均年龄(39.51±13.26)岁(8-67岁)。其中前葡萄膜炎患者35例,男17例,女18例,平均年龄(38.66±12.11)岁。中间葡萄膜炎患者8例,男5例,女3例,平均年龄(37.25±14.92)岁。全葡萄膜炎患者22例,男13例,女9例,平均年龄(41.68±14.69)岁。全葡萄膜炎患者中伏格特-小柳-原田(VKH)综合征患者8例,男4例,女4例,平均年龄(48.88±6.64)岁；Behcet病葡萄膜炎患者4例,男3例,女1例,平均年龄(30.75±17.65)岁。采用糖尿病视网膜病变早期治疗研究组(ETDRS)设计的“E”字型视力表测定远视力。所有患者均在散瞳状态下经裂隙灯显微镜、直接检眼镜以及荧光素眼底血管照影检查和进行诊断分期。诊断和分类标准参照国际葡萄膜炎研究组织(IUSG)分类标准。对全部患者进行血清抗链“O”、类风湿因子、抗核抗体等免疫学检查。同期收集非葡萄膜炎患者25例作为对照组,其中男13例,女12例,平均年龄(45.04±17.41)岁(7-65岁)。所有对照者既往身体健康,近期未服用过抗生素、糖皮质激素或其他免疫抑制剂。所有标本立即置于1.5ml已消毒的硅化离心管中,20℃冰箱保存。应用酶联免疫吸附测定法(ELISA)对所有血清标本进行TNF-α、IL-10和IL-17测定。应用SPSS17.0统计软件对实验数据进行统计学分析,所有患者及对照组的平均年龄和细胞因子水平用均数和标准差(x±s)表示,各种数据经Shapiro-Wilk检验正态分布,经方差齐性检验方差齐。分别采用t检验和卡方检验比较两组人群的年龄和性别之间差异,正态分布数据应用方差分析(F检验)比较各组观察者血清细胞因子水平差异,不属于正态分布的数据应用秩和检验。应用Spearman分析法分析各种细胞因子之间的相互关系,以P<0.05为差异有统计学意义。结果：1.葡萄膜炎发病年龄范围为8-67岁,其中25～44岁患者最多(46.15%),男女比例1.17：1。前葡萄膜炎是葡萄膜炎最常见的类型。明确病因者26例(40%),特发性葡萄膜炎39例(60%)。65例患者中,有28例患者(43.07%)出现各种并发症,致盲率为7.7%。大部分患者经治疗后视力显著提高。2.葡萄膜炎患者组TNF-α、IL-10和IL-17浓度分别为(17.37±12.65)pg/ml、(68.05±111.74) pg/ml和(48.61±35.89) pg/ml;对照组TNF-α, IL-10和IL-17浓度分别为(26.33±12.28)pg/ml、(72.00±129.03)pg/ml和(25.06±28.24)pg/ml。葡萄膜炎患者组TNF-α、IL-17浓度与对照组比较差异有统计学意义(TNF-α:F=9.188/P=0.003; IL-17:P=0.000),IL-10浓度差异无统计学意义(P=0.988)。3.活动期患者TNF-α、IL-10和IL-17浓度分别为(17.99±12.75)pg/ml、(79.15±118.93) pg/ml和(58.01±41.72) pg/ml;稳定期患者TNF-α、IL-10和IL-17浓度分别为(14.33±12.24)pg/ml、(13.54±31.82) pg/ml和(46.18±39.06)pg/ml。活动组TNF-α, IL-10、IL-17血清浓度与稳定期组浓度差异无统计学意义(TNF-α:F=0.762/P=0.386; IL-10:P=0.108; IL-17: P=0.270)。4.前葡萄膜炎组患者血清TNF-α、IL-10和IL-17水平分别为(18.56±13.38)pg/ml、(80.10±113.94) pg/ml和(64.40±42.76) pg/ml;中间葡萄膜炎组患者血清TNF-α、IL-10和IL-17水平分别为(8.41±4.14) pg/ml、(61.05±126.74)pg/ml和(46.81±36.70) pg/ml.全葡萄膜炎组血清TNF-α、IL-10和IL-17水平分别为(18.75±12.40)pg/ml、(51.43±105.49) pg/ml和(46.01±38.95)pg/ml。三组患者血清TNF-α、IL-10和IL-17浓度差异无统计学意义(TNF-α：F=2.393/P=0.100；IL-10：P=0.550；IL-17：P=0.410)。5.应用Spearman相关分析法进行相关分析,结果显示IL-17与疾病呈正相关(Spearman相关系数r=0.371,P=0.000),TNF-α与疾病呈负相关(Spearman相关系数r=-0.301,P=0.004)。结论：1.葡萄膜炎是中青年人群的常见致盲性眼病,其病因复杂,易反复发作,是眼科难治性疾病之一。前葡萄膜炎是最常见临床类型,以特发性葡萄膜炎多见。长期应用传统治疗药物,如糖皮质激素和免疫抑制剂有较大毒副作用。因此,寻找新的治疗方法成为必然。2.葡萄膜炎患者血清中IL-17浓度与对照组比较升高；IL-17是葡萄膜炎的重要细胞因子,表明Th17细胞参与葡萄膜炎的发病。3.葡萄膜炎组血清中IL-10浓度与正常对照组比较无统计学意义,大部分患者血清中IL-10浓度过低无法检测。4.葡萄膜炎组血清中TNF-α浓度低于对照组,抑制TNF-α浓度可能会导致葡萄膜炎发生以及恶化。更多还原

【Abstract】 Objective:1. To observe the clinical features, the complications and treatment effects of uveitis.2. To compare the concentrations of tumor necrosis factor alpha (TNF alpha), interleukin10(IL-10) and interleukin17(IL-17) in serum samples from uveitis (anterior uveitis, intermediate uveitis and panuveitis) patients and normal control group.3. To determine the role of TNF-a, IL-10and IL-17in the pathogenesis of uveitis and to find new treatments.Methods:A series of65patients with uveitis and25healthy persons from our hospital from November2012to May2013were investigated. The cases with uveitis included35males and30females. The age of cases ranged from8to67years, and the mean age was39.51±13.26years. Among the patients with uveitis,35patients with anterior uveitis included17males and18females, and the mean age was38.66±12.11years.8patients with intermediate uveitis included5males and3females, and the mean age was37.25±14.92years.22patients with panuveitis included13males and9females, and the mean age was41.68±14.69years. Among the panuveitis there are8patients with Vogt-Koyanagi-Harada syndrome included4males and4females, and the mean age was48.88±6.64years.4patients with Behcet’s disease included3males and1females, and the mean age was30.75±17.65years. With early treatment diabetic retinopathy research team "E" word eye chart measure far vision. All patients in the specialized state by slit-lamp microscope, direct ophthalmoscope and fluorescein fundus blood vessel according to inspection for diagnosis and staging. Patients measure the serum of antistreptolysin O test, rheumatoid factor, antinuclear antibody and immunological tests. All cases were graded by the classification by the International Uveitis Study Group. In the same period the patients without uveitis collected25cases as control group, included13males and12females, the age of cases ranged from7to65years, and the mean age was45.04±17.41years.25controls who without any history of disease, all the recent not taking antibiotics and corticosteroids or other immune inhibitors were selected into this study. All samples were stored in eppendorf tube at-20℃immediately after obtained. The concentrations of TNF-a, IL-10, IL-17serum samples were measured by enzyme-linked immunosobent assay(ELISA). All data were analyzed with SPSS17.0and concentrations of TNF-a, IL-10, IL-17, the mean age were represented by (mean±standard deviation). The data was coincidence with gauss distribution tested and by Shapiro-Wilk test and the data were regular tested with homogeneity test for variance. The t test and chi-square test were used respectively to compare differences between the two groups of age and gender, F test of variance analysis use to analyze the differences in serum levels of cytokines. Spearman correlation analysis is used to analyze all kinds of relationship between cytokines. The difference was considered with significance when P<0.05.Results:1. The age of cases ranged from8to67years, peak age is around25-44. Gender ratio is1.17for male to female. Anterior uveitis is the most common type. There are26cases with a definite etiology.39cases belong to the idiopathic uveitis. In total65cases,28cases experienced variable complications. There is a7.7%chance leading to blind. After appropriate treatment, most of the patient can get visual function improved.2. The means of TNF-α、IL-10and IL-17concentrations in serum from cases were17.37±12.65pg/ml,68.05±11.74pg/ml and48.61±35.89pg/ml respectively. The mean of TNF-α, IL-10and IL-17concentrations in serum from controls were26.33±12.28pg/ml,72.00±129.03pg/ml and25.06±28.24pg/ml respectively. The difference of TNF-a, IL-17concentrations of serum was statistically significant between cases and controls, IL-10concentrations of serum was not significant difference between cases and controls (TNF-a:F=9.188/P=0.003; IL-10:P=0.988; IL-17:P=0.000).3. The means of TNF-a, IL-10and IL-17concentrations in serum from activity cases were17.99±12.75pg/ml,79.15±118.93pg/ml and58.01±41.72pg/ml respectively. The mean of TNF-a, IL-10和IL-17concentrations in serum from plateau cases were14.33±12.24pg/ml,13.54±31.82pg/ml and46.18±39.06pg/ml respectively. TNF-α, IL-10and IL-17concentrations of serum was no difference between activity cases and plateau cases (TNF-a:F=0.762/P=0.386; IL-10:P=0.108; IL-17:P=0.270).4. The means of TNF-α, IL-10and IL-17concentrations in serum from anterior uveitis were18.56±13.38pg/ml,80.10±13.94pg/ml,64.40±42.76pg/ml respectively. The means of TNF-α, IL-10and IL-17concentrations in serum from intermediate uveitis were8.41±4.14pg/ml,61.05±126.74pg/ml,46.81±36.70pg/ml respectively. The means of TNF-α, IL-10and IL-17concentrations in serum from panuveitis were18.75±12.40pg/ml,51.43±105.49pg/ml and46.01±38.95pg/ml respectively. TNF-a, IL-10and IL-17concentrations of serum was no difference between three groups(TNF-α:F=2.393/P=0.100; IL-10:P=0.550; IL-17:P=0.410).5. Analysis by Spearman correlation test, IL-17was positively related with disease (Spearman correlation coefficient:r=0.371, P=0.000), TNF-a was negatively correlated with disease (Spearman correlation coefficient:r=0.301, P=0.004).Conclusion:1. Uveitis is popular in the young and middle-aged population, a group of common eye disease and is one of blindness worldwide. Anterior uveitis is the most common type. Corticosteroids and immunosuppressive agents are commonly used for the treatment of uveitis. However, long-tenn application of these drugs frequently lead to numerous side effects. Therefore, to find new treatments becomes inevitable.2. IL-17in the serum from uveitis patients increased compared with controls. IL-17is an important cytokine of uveitis. Th17cells may participate in uveitis pathogenesis.3. IL-10in the serum concentration from uveitis patients and controls have no difference, the serum IL-10of majority of patients concentration is too low to be detected.4. TNF-α in the serum from uveitis patients decreased compared with controls. Inhibition of concentration of TNF-a will cause uveitis and deterioration.更多还原