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格雷夫斯病甲亢患者淋巴细胞中葡萄糖和谷氨酰胺的代谢:甲巯咪唑治疗的影响

Metabolism of glucose and glutamine in lymphocytes from Graves' hyperthyroid patients: influence of methimazole treatment.

作者信息

Werner M C, Costa Rosa L F, Romaldini J H, Curi R

机构信息

Department of Endocrinology, Hospital do Servidor Público Estadual, IAMSPE, Butantan, Brasil.

出版信息

Cell Biochem Funct. 1996 Jun;14(2):97-104. doi: 10.1002/cbf.654.

Abstract

Several studies have shown that thyroid hormones are able to influence selected immune responses such as cell mediated immunity, differentiation of B lymphocytes and the activity of NK cells. These hormones can also regulate the metabolism of glucose and glutamine in rat macrophages and their effects seem to occur mainly through the Krebs cycle. Alterations in the hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase and glutaminase activities in lymphocytes from patients with Graves' disease, either untreated or on methimazole (MMI) therapy were investigated. Experiments were also done in vitro to determine the activities of these enzymes in normal lymphocytes cultured for 24 h in the presence of MMI T3 and T4 using concentrations close to the physiological. Changes in the conversion of [U-14C]-glucose and [U-14C]-glutamine to 14CO2 as caused by the addition of MMI, T3 or T4 to the culture medium were also evaluated. The results indicate that high levels of thyroid hormones might stimulate the metabolism of glucose and glutamine for a short period of time but, if the stimulus is maintained, the utilization of glutamine by lymphocytes is then suppressed. Moreover, MMI does affect lymphocyte metabolism but the significance of this finding for its immunosuppressive effect remains to be examined.

摘要

多项研究表明,甲状腺激素能够影响特定的免疫反应,如细胞介导的免疫、B淋巴细胞的分化以及自然杀伤细胞的活性。这些激素还可调节大鼠巨噬细胞中葡萄糖和谷氨酰胺的代谢,其作用似乎主要通过三羧酸循环发生。研究了未经治疗或接受甲巯咪唑(MMI)治疗的格雷夫斯病患者淋巴细胞中己糖激酶、柠檬酸合酶、葡萄糖-6-磷酸脱氢酶和谷氨酰胺酶活性的变化。还进行了体外实验,以确定在接近生理浓度的MMI、T3和T4存在下培养24小时的正常淋巴细胞中这些酶的活性。还评估了向培养基中添加MMI、T3或T4导致的[U-14C]-葡萄糖和[U-14C]-谷氨酰胺向14CO2转化的变化。结果表明,高水平的甲状腺激素可能在短时间内刺激葡萄糖和谷氨酰胺的代谢,但如果刺激持续存在,淋巴细胞对谷氨酰胺的利用随后会受到抑制。此外,MMI确实会影响淋巴细胞代谢,但其这一发现对其免疫抑制作用的意义仍有待研究。

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