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免疫抑制剂静脉冲击治疗Graves病相关性眼病与外周血T淋巴细胞亚群变化的关系
赵卫民1,2,顾明君2*,石勇铨2,陈岚3,邹秀兰1,刘志民2
0
(1.湖北省宜昌市第一人民医院内分泌科,宜昌 443000;2.第二军医大学长征医院内分泌科,上海 200003;3.上海市市北医院内科,上海 200435)
摘要:
目的:探讨免疫抑制剂静脉冲击治疗Graves病相关性眼病(GO)的疗效与外周血T淋巴细胞亚群变化的关系。方法: GO患者58例,随机平均分为2组(n=29),所有患者口服常规抗甲状腺药物和(或)左旋甲状腺素片替代治疗,同时接受含甲泼尼龙0.5 g的生理盐水250 ml及含环磷酰胺0.2 g的生理盐水500 ml静滴,1次/d,连用3 d,间隔4 d重复用,共3~6个疗程。A组在冲击治疗结束后口服泼尼松片和环磷酰胺片,B组在冲击治疗后甲状腺内注射地塞米松磷酸钠注射液。结果:A组中2例退出,B组中1例退出,B组的疗效好于A组(P<0.05)。两组治疗后突眼度、突眼活动度、促甲状腺素受体抗体(TRAb)、过氧化物酶抗体(TPOAb)、外周血NK细胞、CD3+T淋巴细胞、CD8+T淋巴细胞较治疗前明显减少(P<0.05),CD4+/CD8+比值较治疗前升高(P<0.05);B组治疗后突眼度及突眼活动度、CD3+、CD8+ T淋巴细胞较A组降低更显著(P<0.05),CD4+/CD8+比值增高较A组更显著(P<0.05)。治疗前CD4+ T淋巴细胞在显效组、有效组、无效组间存在显著性差异(P<0.05);3组中治疗后的TRAb、TPOAb、CD3+、CD8+T淋巴细胞较治疗前显著减少(P<0.05),CD4+T淋巴细胞、CD4+/CD8+比值治疗后较治疗前显著升高(P<0.05);治疗后TRAb、CD4+、CD8+T淋巴细胞、CD4+/CD8+在3组间存在显著性差异(P<0.05)。结论:甲泼尼龙联合环磷酰胺静脉冲击治疗GO能缓解失调的外周血T淋巴细胞,疗效明显,冲击治疗后甲状腺内注射地塞米松疗效更佳;GO的外周血CD4+ T淋巴细胞降低可能预示疗效不良。
关键词:  Graves病相关性眼病  免疫抑制剂  冲击治疗  外周血  T淋巴细胞
DOI:10.3724/SP.J.1008.2008.00944
投稿时间:2007-10-25修订日期:2008-06-17
基金项目:
Association between intravenous pulse-therapy with immunosuppressant for Graves’ ophthalmopathy and changes of peripheral blood T cell subgroup
ZHAO Wei-min1,2 ,GU Ming-jun2* ,SHI Yong-quan2 ,CHEN Lan2 ,ZOU Xiu-lan1 ,LIU Zhi-min2
(1.Department of Endocrinology,the First People’s Hospital of Yichang,Yichang 443000,China; 2.Department of Endocrinology,Changzheng Hospital,Second Military Medical University,Shanghai 200003;3.Department of Internal Medicine,The Northern City Hospital of Shanghai,Shanghai 200435)
Abstract:
Objective:To study the association between the outcomes of intravenous pulse-therapy with immunosuppressants and the changes of peripheral blood T cell subgroup in patients with Graves’ ophthalmopathy (GO).Methods: Fifty-eight patients with GO were randomized into 2 groups (n=29).All patients received antithyroid drugs orally and (or) Levothyroxine; they also received intravenous meprednisone (0.5 g) and cyclophosphamide(0.2 g) once a day for 3 days.After an interval of 4 days the administration of meprednisone and cyclophosphamide was repeated.All patients received a total of 3-6 times of treatment.Patients in group A were given prednisone and cyclophosphamide orally after immunosuppressants.Patients in group B were injected with Dexamethasone into thyroid after immunosuppressants.Results: Two patients withdrew from group A and one from group B.The therapeutic effect in group B was significantly better than that in group A (P<0.05).Compared with before treatment,the degrees of exophthalmos and exophthalmos activity were significantly lowered after treatment (P<0.05); the thyrotropin receptor antibodies (TRAb) ,thyroid peroxidase (TPOAb),peripheral blood NK cells,CD3+ T lymphocytes,and CD8+ T lymphocytes were significantly reduced after treatment (P<0.05);the ratio of CD4+/CD8+ was increased after the treatment (P<0.05).The degrees of exophthalmos,exophthalmos activity and levels of CD3+ T lymphocytes decreased more significantly in group B than in group A(P<0.05).The ratio of CD4+/CD8+ increased more significantly in group B than in group A(P<0.05).Before treatment the counts of CD4+ T lymphocytes were markedly different between the effective, moderately effective,and the ineffective group (P<0.05).Significant differences in TRAb,TPOAb,CD3+,CD8+ cells were found among the 3 groups after treatment.(P<0.05).CD4+ T lymphocytes and CD4+/CD8+ ratio were significantly higher after treatment compared with those before treatment (P<0.05).Significant differences in TRAb,CD4+,CD8+ T lymphocytes,CD4+/CD8+ ratio were found among 3 groups (P<0.05).Conclusion: Combination of meprednison and cyclophosphamide can relieve the abnormality of peripheral blood T cells in GO and has obvious therapeutic effect.Additional intrathyroid injection of dexamethasone may achieve even better outcome.The reduction of CD4+ T lymphocytes in peripheral blood of GO patients may indicate poor prognsis.
Key words:  Graves’ ophthalmopathy  immunosupressant  bolus therapy  peripheral blood  T lymphocytes