甲状腺功能亢进代偿对Graves病患者血液中性粒细胞化学发光和酶活性的影响

M. Dudina, A. Savchenko, S. Dogadin, I. Gvozdev
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引用次数: 0

摘要

背景:Graves病的氧化应激可增强中性粒细胞的细胞毒性并支持自身免疫性炎症。仅在某些情况下,用噻马唑保守治疗消除甲亢导致缓解,这决定了在治疗疾病的病因治疗方法中寻找免疫标记物的必要性。目的:研究甲状腺功能亢进代偿型Graves病患者外周血中性粒细胞的化学发光和酶活性,以确定免疫治疗的细胞内靶点。材料和方法:使用36通道化学发光分析仪«BLM-3607»(MedBioTech,克拉斯诺亚尔斯克)评估自发和酵母菌诱导的化学发光。外周血中性粒细胞的反应性表征为:Tmax -化学发光反应的发生速率,Imax -最大活性氧(ROS)合成水平和化学发光曲线下面积(S -测量90分钟内ROS的总合成)。采用生物发光法测定了中性粒细胞中NAD(P)依赖性脱氢酶的活性。结果:前瞻性研究纳入126例Graves病患者,年龄18 ~ 65岁,其中代偿性甲亢93例(73.81%),非代偿性甲亢33例(26.19%)。在非代偿性甲状腺机能亢进患者中,自发ROS和酶生酶诱导的lucigenin依赖性化学发光指标S相对于对照组和代偿性甲状腺机能亢进患者均显著升高。复发性甲状腺功能亢进患者在鲁米诺依赖性化学发光期间的抗原中性粒细胞刺激显示,ROS的总合成比对照组增加了十倍以上,但与代偿性甲状腺功能亢进患者无统计学差异。复发性甲状腺机能亢进患者NADH-GDG水平较高,无论是相对于对照范围还是相对于甲状腺功能亢进患者。结论:甲亢患者外周血中氧中性粒细胞代谢紊乱主要影响ROS的产生,这与甲亢代偿及噻马唑的免疫抑制作用有关。在复发性甲亢患者中,不仅在初始氧化反应阶段,而且在继发性ROS水平上,高能氧化剂的产生都发生了更多的变化,表明细胞反应免疫机制的激活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The chemiluminescent and enzymatic activity of blood neutrophils in patients with Graves' disease depending on hyperthyroidism compensation
BACKGROUND: Oxidative stress in Graves’ disease can potentiate the cytotoxicity of neutrophils and support autoimmune inflammation. Elimination of hyperthyroidism with conservative therapy with thiamazole only in some cases leads to remission, which determines the necessity to search an immunological markers for etiotropic therapeutic approaches in treatment of the disease.AIM: To study the chemiluminescent and enzymatic activity of peripheral blood neutrophils in patients with Graves’ disease depending on hyperthyroidism compensation to determine the intracellular targets of immunotropic treatment.MATERIALS AND METHODS: Spontaneous and zymosan-induced chemiluminescence was evaluated using a 36-channel chemiluminescence analyzer «BLM-3607» (MedBioTech, Krasnoyarsk). The reactivity of peripheral blood neutrophils was characterized by: Tmax — the rate of development of the chemiluminescent reaction, Imax — the maximum level of reactive oxygen species (ROS) synthesis and the area under the chemiluminescence curve (S — total synthesis of ROS for 90 minutes of measurement). The activity of NAD(P)-dependent dehydrogenases in neutrophils was determined using the bioluminescent method.RESULTS: The prospective study included 126 women with Graves’ disease, aged 18 to 65 years, 93 (73.81%) with compensated and 33 (26.19%) with uncompensated hyperthyroidism. In uncompensated hyperthyroidism, the indicator S of spontaneous ROS and zymosan-induced lucigenin-dependent chemiluminescence increases significantly, both relative to the control and to the values of compensated hyperthyroidism patients. Antigenic neutrophils stimulation during luminol-dependent chemiluminescence in patients with recurrent hyperthyroidism demonstrated more than tenfold increase in the total synthesis of ROS relative to the control, but no statistically significant differences with compensated hyperthyroidism patients. A high level of NADH-GDG was established in patients with recurrent hyperthyroidism, both relative to the control range and to the patients with euthyroidism.CONCLUSION: Violation of oxygen peripheral blood neutrophils metabolism in patients with euthyroidism mainly affects the production of ROS, which is associated with hyperthyroidism compensation and the immunosuppressive effect of thiamazole. In patients with recurrent hyperthyroidism, there are more changes in the production of high-energy oxidants not only at initial oxidative reactions stage, but also at the level of secondary ROS, indicating the activation of cellular response immunological mechanisms.
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