Graves病多发家系成员甲状腺自身免疫状况及碘摄入量对其发病率的影响

目的：确定在Graves病（GD）多发家系成员中,甲状腺自身免疫及甲状腺功能异常的发生情况,并研究碘摄入量对GD发病率的影响。方法：对全部家系成员做甲状腺疾病病史询问,体格检查,甲状腺功能及甲状腺自身抗体测定,并测定空腹尿碘含量。结果：GD患者一级亲属的亚临床甲亢,临床甲状,亚临床甲状的患病率分别为5．2％,1．0％和1．4％,这三种疾病患者的甲状腺自身抗体均为阳性,甲状腺功能正常一级亲属的甲状腺自身抗体阳性率为68．6％,尿碘水平500－599ug/L时,GD的发病率显著增高（P＜0．05）,。结论：在GD多发家系中,GD患者一级亲属发生甲状腺功能异常的原因均为自身免疫甲状腺病,尿碘水平500－599ug/L是GD发病率增高的危险因素。     

Graves' disease and autoimmune thrombocytopenic purpura: distinct outcomes of the two diseases

The association of idiopathic thrombocytopenic purpura and Graves' disease is rare. Hence, little is known about the outcomes of these two diseases when associated. We report two cases of idiopathic thrombocytopenic purpura associated with Graves' disease, in which the two diseases had distinct outcomes. Thus, the hypothesis of cross-reaction between antithyroid antibodies and platelet epitopes, which has been proposed to explain the association, seems unlikely.     

家族性Graves病55例临床分析

目的 分析家族性Graves病（GD）的临床特征,并与同期住院的非家族性GD进行比较。方法 对同期住院的55例家族性GD和471例非家族性GD的临床特征进行回顾性对比分析。结果 家族性GD约占全部GD的10％;病程较长;男女患病机会相等;复发和发生浸润性突眼的相对危险度分别是非家族性GD的2.3倍和2.1倍。结论 家族性GD具有男女患病机会一致、容易复发、病程较长等临床特征。     

沙利度胺对Graves病甲状腺功能的影响18例临床观察

选择2006年8月至2009年3月宁波市第二医院内分泌科收治的Graves病患者18例,随机分为抗甲状腺药物单药组10例(单药组)及沙利度胺与抗甲状腺药联合组(联合组)8例。比较治疗前及治疗3、6周后患者甲状腺功能。     

诱导新生小鼠对Graves病免疫耐受的研究

目的 研究TSH受体(TSHR)289基因诱导Graves病新生免疫耐受的可行性,并初步探索其可能机制.方法 将出生0～24hBALB/c雌性小鼠分为腹腔注射组、肌肉注射组、造模组及正常对照组,腹腔注射组或肌肉注射组分别设低剂量、中剂量、高剂量耐受组及相应对照组,将腹腔注射、肌肉注射不同剂量耐受组及各自对照组给予1×106particles(低)、1×108particles(中)、1×1010particles(高)的Ad-TSHR289或Ad-lacz进行预处理6～7周后,除正常对照组肌肉注射Ad-lacz外,其余各组小鼠均给予Ad-TSHR289免疫,每3周1次,共3次,首次免疫后10d检测血清促甲状腺素受体抗体(TRAb),末次免疫后4周测血清TRAb、TT4、脾CD4+CD25+Foxp3/CD4+比例,并行甲状腺组织学检查.结果 首次注射后10d,腹腔注射及肌肉注射高剂量耐受组均未诱导出针对TSHR的抗体反应,而对照组TRAb滴度明显升高(P＜0.05).末次免疫后4周,腹腔及肌肉注射高剂量耐受组均只有1/10小鼠出现阳性的抗体反应,腹腔注射高剂量耐受组没有小鼠发生甲状腺功能亢进,而肌肉注射高剂耐受量组2/10小鼠出现轻微的TT4升高,其相应对照组却出现了强烈的抗体反应(P＜0.01),TT4水平明显升高(P＜0.05),所有TT4升高的小鼠均出现了甲状腺组织增生性改变.此外,腹腔注射及肌肉注射高剂量耐受组CD4+CD25+Foxp3/CD4+比例与对照组比较明显增高(P＜0.01)腹腔注射及肌肉注射其余组群,与其对照组和造模组比较Graves病发生率差异无统计学意义.结论 TSHR 289基因可以通过腺病毒为载体,腹腔和肌肉注射两种途径诱导新生小鼠成年后对Graves病免疫耐受,抑制Graves病的发生.而高剂量的抗原刺激容易导致耐受产生.CD4+CD25+Foxp3+T细胞在免疫耐受的诱导和维持中可能起重要作用.     

弥漫性甲状腺肿伴甲状腺功能亢进症致病易感基因识别鉴定研究的现状

经过半个世纪对弥漫性甲状腺肿伴甲状腺功能亢进症(Graves’disease,GD,甲亢)候选基因在小样本人群中的研究,提供了不少相互矛盾的结果.在这些研究中,仅仅证实主要组织相容性复合物(MHC)是甲亢的一个致病易感位点,因为这个位点对甲亢发生影响较大.应用以低密度的微卫星标志进行全基因组连锁分析,虽然发现了一些甲亢的致病易感区段,但并未能识别真正的甲亢致病易感基因.随后由于大量单核苷酸多态性(SNP)的发现及其标签SNP(Tag SNP)技术的出现,人们对候选基因上的Tag SNP在大样本人群中的分析,发现了一些真正的甲亢致病易感基因,包括免疫相关的基因如MHC、CTLA4、SCGB3A2/UGRP1和FCRL3以及一个甲状腺特异的基因TSHR(促甲状腺素受体基因).同时,也发现了一些还有争议但需要进一步证实的甲亢易感基因如PTPN22和甲状腺球蛋白基因等.在不久的将来,全基因组关联分析和全基因组再测序技术,在甲亢易感基因识别鉴定中的应用,无疑将会促进大量甲亢易感基因的发现,加深人们对甲亢发病机制的理解.     

Antioxidative action of royal jelly in the yeast cell

Royal jelly is a bee product, secreted from the hypopharingeal and mandibular glands of worker bees. There are many reports on pharmacological activities of royal jelly in experimental animals, but there are few about its antioxidative properties connected to aging. The aim of the work was to investigate the antioxidative action of royal jelly in the cell of the yeast Saccharomyces cerevisiae as a model organism. Yeast was cultivated in YEPD medium enriched with different concentrations of royal jelly like 1, 2 and 5 g/L. Yeast growth was monitored by measuring optical density. At different time points cell energy metabolic activity was measured using the cell energy metabolism indicator resazurin, and 2',7'-dichlorofluorescein was applied to estimate intracellular oxidation. Additionally, protein profile of cell extract was analyzed by 2-D electrophoresis. Results showed that royal jelly decreased intracellular oxidation in a dose dependent manner. Additionally it affected growth and cell energy metabolic activity in a growth phase dependent manner. Protein profile analysis showed that royal jelly in the cell does not act only as a scavenger of reactive oxygen species, but it also affects protein expression. Differentially expressed proteins were identified.     

Graves病患者血清氨基端-脑钠肽前体水平的变化

目的 研究Graves病(GD)甲亢患者血清氨基端.脑钠肽前体(NT-proBNP)的变化特点及临床意义.方法 入选GD患者269例,其中初发患者90例.测定血清甲状腺激素、促甲状腺素受体抗体(TRAb)和NT-proBNP水平.结果 血清NT-pmBNP与FT3(r=0.260,P<0.01)、FT4(r=0.297,P<0.01)和心率正相关(r=0.251,P<0.05);与超敏TSH(sTSH)负相关(r=-0.157,P<0.01).校正年龄、性别和体重指数(BMI)后,血清NT-pmBNP仍与FT3、FT4和TRAb正相关(均P<0.01).校正血清FT3,FT4、sTSH、TRAb、年龄、性别、BMI后,初发组和治疗组的血清NT-proBNP差异仍有统计学意义(P<0.01),血清FT4对NT-pwBNP有显著影响(P<0.01),NT-proBNP水平的升高在甲亢已经控制的患者中同样存在.结论 GD患者血清NT-pwBNP水平随着FT4的升高而明显上升,不受性别、年龄和BMI的影响.监测血清NT-pmBNP有助于了解GD患者的血管僵硬度和容量变化,为早期防治甲亢引起的心血管疾病提供依据.     

丙基硫氧嘧啶与甲巯咪唑对Graves病患者细胞因子的影响

将64例Graves病(GD)患者分为甲巯咪唑组(MMI,n=30)和丙基硫氧嘧啶组(PTU,n=34),20名健康志愿者作为对照组.采集各组患者治疗前、治疗后3、6个月血清,分别用酶标记免疫吸附法检测血浆白细胞介素(IL)-2、IL-6及促甲状腺素受体抗体(TRAb)的水平.结果显示,2组治疗前一般情况比较差异无统计学意义.2组用药后6个月IL-2、IL-6水平较治疗前差异均有明显统计学意义(P＜0.05),随时间延长IL-2逐渐升高,IL-6逐渐降低;用药6个月后MMI组IL-6水平较PTU组明显降低(P＜0.05).2组治疗前TRAb水平无显著差异,2组治疗后3和6个月TRAb差异均有统计学意义(均P＜0.01),随时问增加逐渐下降.IL-2/IL-6比值在同一组治疗3、6个月后均较治疗前明显升高(P＜0.05).治疗6个月后MMI组较PTU组更高(P＜0.05).GD治疗前血清中IL-6水平与FT3、FT4呈正相关,IL-2水平与FT3、FT4和TRAb呈负相关;治疗3、6个月后,IL-2、IL-6与FT3、FT4无明显相关性;MMI组治疗前后IL-2、IL-6水平均与TRAb相关.这些结果提示,MMI较PTU更具有改善GD患者自身免疫的作用.     

不同治疗方法对Graves病患者外周血淋巴细胞亚群的影响

目的 探讨抗甲状腺药物、131I、外科手术对Graves病患者外周血淋巴细胞亚群的影响.方法 选取106例符合Graves病诊断的门诊及住院患者,根据患者实际情况分为抗甲状腺药物组(39例)、131I治疗组(48例)、甲状腺次全切除术组(19例),于治疗前及治疗后3、6、12个月采用化学发光免疫仪检测游离T3、游离T4、促甲状腺激素(TSH)水平.电化学发光仪检测TSH受体抗体(TRAb).流式细胞术检测CD3+、CD3+ CD4+、CD3+CD8+、CD3/(CD16+CD56+)、CD3-CD19+等水平.结果 治疗后3个月,与其他两组相比,甲状腺次全切除术组游离T3、游离T4、TRAb水平降低,TSH水平升高(F=52.95～126.81,P均＜0.05).治疗后6个月,131I治疗组与抗甲状腺药物组相比,游离T3水平有降低趋势,但无统计学意义(P＞0.05),游离T4、TSH无明显差异(P均＞0.05),而TRAb水平的变化有统计学意义(F =42.69,P＜0.05).治疗后12个月,各治疗组游离T3、游离T4、TSH、TRAb趋向正常水平.治疗前,3组患者CD3+、CD3+ CD4+、CD3+CD8+、CD4+/CD8+、CD3/(CD16+CD56+)、CD3-CD19+的差异元统计学意义.治疗后各时间点,与其他两组相比,甲状腺次全切除术组CD3+、CD3+ CD4+、CD3+CD8+、CD4+/ CD8+水平均最低(F =3.48～68.28,P均＜0.05);与抗甲状腺药物组相比,治疗3个月后,131I治疗组CD3+、CD3+CD4+、CD3+CD8+、CD4+/CD8+、CD3-CD19+明显升高(F =13.85～68.28,P均＜0.05),随着治疗时间的延长各指标逐渐降低.相关性分析表明,游离T3、游离T4、TRAb与CD3+(r=0.319,0.402,0.426,P均＜0.01)、CD3+CD4+(r =0.467,0.526,0.453,P均＜0.01)、CD3-CD 19+(r =0.493,0.462,0.241,P＜0.01)呈正相关,与CD3+CD8+ (r=-0.422,-0.523,-0.344,P均＜0.01)、CD3 (CD16+CD56+)(r=--0.597,-0.543,-0.487,P均＜0.01)呈负相关.TSH与CD3+CD8+、CD3(CD16+CD56+)(r=0.436,0.474,P均＜0.01)呈正相关,与CD3+、CD3+CD4+、CD3-CD19+(r =-0.360,-0.522,-0.530,P均＜0.01)呈负相关.结论 不同的治疗方法对Graves病患者外周淋巴细胞亚群产生不同的影响,检测外周淋巴细胞亚群的水平对Graves病的治疗有一定的指导意义.     

Comparison of standardized initial doses of two antithyroid drugs in the treatment of Graves' disease

Objectives. To obtain a simple standard regimen, suitable for general practice, and based upon the addition of antithyroid drug plus thyroxine for attaining euthyroidism in patients with Graves' disease. Design. Prospective, randomized trial of patients with Graves' disease followed for 3 months after the initiation of therapy with an antithyroid drug and combined with the later addition of triiodothyronine to keep the patient euthyroid. The patients were randomized, according to birth date, between methimazole and propylthiouracil. Three dose schemes were tested for each antithyroid drug. Setting. The study was performed at the thyroid outpatient units of two general hospitals, with the patients having been referred from primary care. Subjects. Ninety-four patients with Graves' disease who were suitable for treatment with antithyroid drugs. Interventions. The patients were allocated into six groups. Three groups received methimazole (10 mg every 6th, 8th or 12th h) and three received propylthiouracil (100 mg every 6th, 8th or 12th h). Twenty micrograms of triiodothyronine was added when the patients were euthyroid to avoid hypothyroidism. Main outcome measures. The lowest serum free thyroxine level within 3 months of the initiation of the antithyroid treatment. Results. Fourteen per cent of the patients on methimazole 10 mg every 12th h and 29% on propylthiouracil 100 mg every 12th h did not achieve euthyroidism within the 3-month observation period. All but one patient on methimazole 10 mg every 8th h or propylthiouracil 100 mg every 8th h reduced the free serum thyroxine levels to the normal or hypothyroid range within the observation period. All of the patients on methimazole 10 mg every 6th h and 56% on propylthiouracil 100 mg every 6th h reduced the serum T4 values into the hypothyroid range within the period. Conclusion. A standard regimen, based upon the addition of methimazole 10 mg every 8th or 6th h or propylthiouracil 100 mg every 8th or 6th h and followed by the addition of thyroxine or triiodothyronine when euthyroid to avoid hypothyroidism, seems to be suitable for attaining euthyroidism within 3 months in patients with Graves' disease. A dose scheme based on methimazole 10 mg every 12th h or propylthiouracil 100 mg every 12th h were found to be unsuitable due to an unacceptably high incidence of failure to attain euthyroidism or hypothyroidism within 3 months.     

桥本甲状腺功能亢进与Graves病鉴别诊断的临床观察

目的 探讨细针穿刺细胞学(FNAC)检查和甲状腺自身抗体检测在桥本甲状腺功能亢进(甲亢)与Graves病(GD)鉴别诊断中的临床应用价值.方法 本组资料362例中有3例因样本细胞数量少而未能诊断,根据FNAC分型将359例甲亢患者分为桥本甲亢组119例、GD-Ⅰ组(间质淋巴细胞浸润<10%)162例、GD-Ⅱ组(淋巴细胞浸润10%～20%)49例、GD-Ⅲ组(淋巴细胞浸润20%～40%)29例,观察4组甲状腺自身抗体及甲状腺激素水平的差异.结果 FNAC发现淋巴细胞破坏上皮细胞以及退行性变和(或)嗜酸性变的滤泡上皮细胞时仅见于桥本甲亢组,为其特征性表现.GD-Ⅰ、Ⅱ、Ⅲ3组FNAC检查可见淋巴细胞数量依次呈增加趋势,而滤泡上皮细胞增生呈降低趋势;3组平均血清甲状腺球蛋白抗体(TGAb)分别为(43.5±29.0)%、(61.3±24.4)%、(68.9±22.3)%,而平均甲状腺微粒体抗体(TMAb)分别为(38.0±26.1)%、(54.7±23.0)%、(60.8±22.7)%,与GD-Ⅰ组相比,GD-Ⅱ、GD-Ⅲ组升高均有显著性差异(P<0.05);3组的促甲状腺激素受体抗体(TRAb)水平分别为(57.7±71.0)U/L、(31.5±62.1)U/L、(21.2±47.0)U/L,与GD-Ⅰ组相比,GD-Ⅱ、GD-Ⅲ组显著降低(P<0.01).桥本甲亢组TGAb、TMAb均值显著高于GD-Ⅰ组(P<0.01),而TRAb、游离T_3(FT_3)、游离T_4(FT_4)均值显著低于GD-Ⅰ组(P<0.01);桥本甲亢组与GD-Ⅱ、Ⅲ组相比,各抗体均值差异均无统计学意义(P>0.05).GD-Ⅲ组病史均值显著长于其他3组(P<0.01),而其他3组间差异无显著性(P>0.05).结论 FNAC对鉴别桥本甲亢与GD各型具有重要的临床价值.血清TRAb、TGAb、TMAb水平对鉴别桥本甲亢与GD-Ⅰ型有一定临床价值,而对鉴别桥本甲亢与GD-Ⅱ型、Ⅲ型临床意义不大.     

Graves病甲状腺共刺激分子GL50-ICOS的表达及其免疫病理意义

目的 研究共刺激分子GL50-ICOS在Graves病(GD)甲状腺组织中的表达及其免疫病理意义.方法运用细胞培养、流式细胞术、RT-PCR、Western印迹和免疫组化技术,检测GD甲状腺组织和原代培养的甲状腺滤泡细胞(TFC)共刺激分子GL50和ICOS的表达.结果 (1)与正常同龄对照相比,CD4+CD28-T细胞群体在GD患者外周血中显著升高,其表面ICOS表达上调.(2)RT-PCR显示,GD患者甲状腺组织中有ICOS mRNA表达,与对照非毒性甲状腺肿(NTG)组相比具有统计学差异(P＜0.01).(3)Western印迹显示,GL50蛋白在10例GD患者组织中全部表达,较对照组差异有统计学意义(P＜0.01).(4)与对照甲状腺腺瘤组相比,GL50在20例GD患者组织切片中全部检出,而对照组无阳性表达(P＜0.01).(5)炎性细胞因子刺激体外原代培养的甲状腺滤泡细胞表面上调表达GL50(P＜0.05).结论共刺激分子GL50-ICOS在Graves病甲状腺组织异常表达.     

Determination of oxidative stress in thyroid tissue and plasma of patients with Graves' disease

BACKGROUND: The aim of our study was to evaluate the oxidant/antioxidant status of thyroid tissue in Graves' disease (GD) patients and to compare the results of GD thyroid tissue with plasma of patients and healthy controls. METHODS: We studied 25 consecutive patients with GD hyperthyroidism who underwent surgical treatment. The patients were divided into groups according to the duration of antithyroid drug treatment, the type of antithyroid drugs used, the presence of ophthalmopathy, and recurrence after a complete course of antithyroid drugs. Thiobarbituric acid-reacting substances (TBARS), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, and total thiol (t-SH) content of tissue and plasma samples were determined. RESULTS: TBARS concentrations were found to be significantly increased in GD patients' plasma compared with controls' plasma (0.1+/-0.02 nmol/mg protein vs. 0.062+/-0.01 nmol/mg protein). Significantly decreased t-SH concentrations were measured in GD patients' plasma compared with controls (8.26+/-1.9 nmol/mg protein vs. 13.03+/-3.3 nmol/mg protein). Tissue TBARS, t-SH, GPx, and SOD measurements in GD patients indicated significantly increased concentrations compared with the plasma levels of patients. Patients with shorter treatment duration before the operation had significantly increased plasma and tissue TBARS and decreased plasma and tissue t-SH concentrations. Patients on propylthiouracil treatment had significantly lower plasma and tissue concentrations of TBARS than patients on methimazole. Patients with recurrence had significantly higher plasma and tissue TBARS and lower plasma and tissue t-SH concentrations than patients treated for the first time. CONCLUSIONS: In euthyroid GD patients on antithyroid drugs, increased oxidative stress and a compensatory increase in the antioxidant defense system are more prominent in thyroid tissue than in plasma. Patients who relapsed had markers indicating increased oxidative stress. Thus, ongoing autoimmunity may contribute to increased oxidative stress in GD patients, even in the euthyroid state.     

他巴唑和甲状腺素对Graves'病患者sIL-2R的影响

研究他巴唑和甲状腺素对Ｇｒａｖｅｓ’病患者ｓＩＬ－２Ｒ的影响。方法将２５例Ｇｒａｖｅｓ’病患者外周血单个细胞在不同浓度的他巴唑和甲状腺素条件下进行体外增减同时检测培养上清液及血浆ｓＩＬ－２Ｒ水平并与血浆游离Ｔ３（ＦＴ３）和游离Ｔ４（ＦＴ４）作相关分析。结果ＧＤ患者血浆ｓＩＬ－２Ｒ较正常对照明显升高,并与血浆ＦＴ３和ＦＴ４成正相关（分别为（Ｐ〈０．０５和Ｐ〈０．０１）;ＧＤ患者ＰＢＭＣ培养上清ＳＩＬ     

三种不同方法治疗Graves病的疗效和预后分析

目的 研究药物、手术、放射性碘治疗三种方法对Ｇｒａｖｅｓ病（ＧＤ）的有效率、复发率及其相关性。方法 采用回顾性调查方法,分析２１２例ＧＤ患者的治疗情况及预后。结果 治疗停止半年后治愈率分别为药物组７８．６％、手术组９１．９％、放疗组９５．２％,治疗后５年治愈率分别为药物组５４．５％、手术组９０．６％、放疗组８１．８％。结论 治疗后半年及５年药物组治愈率均低于手术组和放疗组,而复发率则相反。药物组有     

表达人TSHR的腺病毒诱导Graves病小鼠模型的研究进展

利用表达人促甲状腺激素受体(TSHR)或TSHR A亚单位的重组腺病毒免疫BALB/c小鼠,诱导Graves病(GD)动物模型是一种稳定的建模方法.本综述总结了该模型本身的特点和发展,遗传、环境因素对GD模型的影响以及制作GD模型的过程中B淋巴细胞、调节性T淋巴细胞和辅助性T细胞(Th)1/Th2免疫平衡所起的作用.为探讨GD发生机制和寻找新的治疗方法提供了很好的启示.     

肠上皮屏障功能的调节与自身免疫性疾病的关系

近年来研究发现很多自身免疫性疾病与肠上皮屏障的功能密切相关,本文着重对肠上皮屏障的基本结构、调控及与自身免疫性疾病的关系作一综述。     

Graves眼病Th1/Th2相关细胞因子群谱的特征

目的　探讨Graves眼病 (Graves’ophthalmopathy ,GO)发生的免疫机制 ,明确GO的Th1/Th2 相关细胞因子群谱的特征。方法　用逆转录聚合酶链反应 (RT PCR)检测IFN γ、TNF α、IL 2、IL 4、IL 6、IL 10等 6种细胞因子的mRNA转录。结果　与正常对照组相比 ,Graves病恶性突眼组与非突眼组细胞因子的基因转录检出率明显增高 (P <0 .0 1) ;Graves病非突眼组Th2 类细胞因子IL 4和IL 6的基因转录检出率明显高于Th1类细胞因子IFN γ ,TNF α和IL 2的基因转录检出率 (P <0 .0 1) ;而恶性突眼组Th1和Th2 之间细胞因子的基因转录检出率差异无显著性 (P >0 .0 5 )。结论　Graves病恶性突眼者细胞因子的基因转录模式呈典型的Th0 ,细胞免疫和体液免疫共同参与了突眼的发生 ,而非突眼者细胞因子表达向Th2 方向漂移 ,以体液免疫应答为主。     

Graves病131I治疗前和治疗一年中促甲状腺素受体抗体水平的动态变化

对157例Graves病131I门诊治疗的病例进行回顾性研究.按131I治疗1年后甲状腺功能状态分成3组:缓解组(FT3、FT4)、部分缓解组(FT3、FT3未降至正常范围)、甲减组(FT3、FT3低于正常).治疗前促甲状腺素受体抗体(TRAb)的阳性率为88.5%.131I治疗后,TRAb在3～6个月时达高峰,之后逐渐下降.甲状腺重量、显著升高的TRAb(≥405 U/L)、FT3、FT3水平是评估预后的指标.