Background Insulin-like growth factor-1 (IGF-1) participates in the regulation of the biological activity of cells.Researches showed that the serum IGF-1 level is significantly raised in the patients with Graves diseases.Thyroid associated ophthalmopathy (TAO) is one of Graves diseases,and orbital adipose cells are the target cells of thyroid autoantigens.However,whether IGF-1 is associated with TAO is still unclear.Objective This study was to investigate the expressions of IGF-1 in both circulating blood and orbital adipose tissue in TAO patients.Methods A retrospective cohort study was performed.Eighty-six TAO patients were enrolled in West China Hospital of Sichuan University from August 2009 to February 2014.According to the clinical activity score criteria(CAS) ,the patients were divided into active stage (CAS ≥ 4,35 patients) and inactive stage (CAS ＜4,51 patients).Eighty-six health adult persons were enrolled as the controls.The periphery blood of 3 ml was collected from each subject to detect the serum IGF-1 level by ELISA.Orbital adipose tissues were obtained during the surgery from 35 TAO patients and 35 patients with benign orbital tumor or orbital adipose prolapse from August 2009 to February 2014.The histopathological examination of orbital adipose tissue was carried out to evaluate the pathological characteristics, and the expression of IGF-1 in orbital adipose tissue was assessed by immunochemistry.This study protocol was approved by Ethic Committee of West China Hospital of Sichuan University, and informed consent was obtained from each subject before entering the cohort.Results The mean serum IGF-1 level was (0.862±0.026)ng/ml in the TAO patients,and that in the normal controls was (0.767 ± 0.480) ng/ml, without significant difference between them (P=0.281).The mean serum IGF-1 level was (0.877±0.355) ng/ml and (0.803±0.031) ng/ml in active stage and inactive stage of patients, respectively, and no significant difference was found between them (P =0.834).IGF-1 expression located in cellular membrane and cytoplasm.The expressing intensity of IGF-1 in orbital adipocytes was significantly enhanced in the TAO patients with the positive rate of 74.29% , and that in the controls was 45.46％ ,showing a statistical difference between the two groups (x2=5.289,P=0.021).Conclusions Serum IGF-1 level dose not rise in TAO patients, but the expression of IGF-1 in orbital adipocytes up-regulates, indicating that mature orbital adipocytes of TAO are regulated mainly by IGF-1.%背景 胰岛素样生长因子-1(IGF-1)参与细胞的分裂、增生、分化或凋亡调控过程,已证实Graves病患者血清1GF-1水平升高.甲状腺相关眼病(TAO)是Graves病在眼部的表现,眼眶脂肪细胞是甲状腺自身抗原的靶细胞,IGF-1是否参与TAO的发病是研究的方向之一. 目的 研究TAO患者外周血及眼眶脂肪组织中IGF-1的表达变化.方法 采用回顾性研究方法,纳入2009年8月至2014年2月于四川大学华西医院眼科就诊的TAO患者86例作为TAO患者组,按照临床活动性评分法(CAS)及TAO严重度分级法进行TAO活动度分期,CAS≥4分者35例(活动期组),CAS＜4分者51例(非活动期组).同期纳入年龄和性别匹配的眼外伤或白内障患者86例作为对照组.采集所有患者肘静脉血3 ml,采用ELISA法测定血清中IGF-1的质量浓度.采集TAO患者组中行眼眶减压术-部分眶脂肪切除术的35例患者的眼眶脂肪组织作为TAO标本组,同时收集35例眼眶良性肿瘤或眼眶脂肪脱垂患者的眼眶脂肪组织作为标本对照组.将眼眶脂肪组织制备组织切片,分别行组织病理学检查和免疫组织化学染色,观察TAO患者眼眶脂肪组织的病理学特征,检测眼眶脂肪组织中IGF-1的表达情况. 结果 TAO患者组和对照组外周血IGF-1质量浓度分别为(0.862±0.026) ng/ml和(0.767±0.480) ng/ml,TAO患者组患者外周血IGF-1质量浓度高于对照组,但差异无统计学意义(P=0.281).TAO患者活动期组和非活动期组血清IGF-1质量浓度分别为(0.877±0.355)ng/ml和(0.803±0.031) ng/ml,组间比较差异无统计学意义(P=0.834).免疫组织化学检测可见IGF-1主要表达于脂肪细胞膜和细胞质,TAO标本组可见IGF-1表达呈深褐色着染,细胞强阳性率为74.29％,标本对照组为浅棕色着色,细胞强阳率为45.46％,差异有统计学意义(∥=5.289,P=0.021). 结论 TAO患者外周血中IGF-1水平并无明显升高,且患者外周血中IGF-1水平的改变与病变程度无明显关联.IGF-1在局部眼眶脂肪组织中表达量明显增加,可能与患者眼眶脂肪组织的增生有关.
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