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目的 探讨抗甲状腺药物的作用机制。方法 ①在甲状腺过氧化物酶(TPO)中加入他巴唑、碘化钾、过氧化氢,然后进行透析,用3,3,5,5,四甲基联苯胺(TMB)测TPO的活性;②在TPO催化酪氨酸碘化的反应体系中,加入他巴唑,并逐渐增加过氧化脲的浓度,观察过氧化脲浓度对他巴唑干扰酪氨酸碘化的影响。结果 TPO中加入他巴唑,与加入磷酸盐缓冲液(PB)对照,经透析后,两者酶活性没有明显的区别。在TPO催化的酪氨酸碘化的反应体系中,提高过氧化脲的浓度,能抵消他巴唑对酪氨酸碘化的抑制作用。结论 他巴唑对TPO无直接抑制作用,其作用机制是夺去酪氨酸碘化所必需的活性氧(他巴唑本身被氧化)从而抑制甲状腺素的合成。
Objective To explore the mechanism of antithyroid drugs. Methods ①Thompatazole, potassium iodide and hydrogen peroxide were added to the thyroid peroxidase (TPO), then dialyzed, and the activity of TPO was measured by using 3,3,5,5-tetramethylbenzidine (TMB) ② In TPO catalyzed tyrosine iodination reaction system, methimazole was added and the concentration of carbamide peroxide was gradually increased to observe the effect of carbamide concentration on tyrosine iodide interference. Results Adding methimazole to TPO and adding phosphate buffer solution (PB), there was no significant difference between the two enzymes after dialysis. In the TPO-catalyzed tyrosine iodination reaction system, increasing the concentration of urea peroxide can counteract the inhibitory effect of methimazole on tyrosine iodide. CONCLUSION Methimazole has no direct effect on TPO. Its mechanism of action is to depress the synthesis of thyroxine, which is necessary for the activation of tyrosine iodide (methimazol itself is oxidized).