胺碘酮对SD大鼠甲状腺功能及形态影响的实验研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (5): 508-512.

胺碘酮对SD大鼠甲状腺功能及形态影响的实验研究

江力勤¹, 王志刚², 季玉珍²

¹浙江省嘉兴市第二医院心内科, ²科教科,嘉兴 314000,浙江

收稿日期:2012-02-03 修回日期:2012-04-28 出版日期:2012-05-26 发布日期:2012-05-28
通讯作者: 王志刚,男,主任检验师,硕士生导师,研究方向:主要从事临床免疫学及实验诊断。Tel: 0573-82056643 E-mail: xie303@126.com
作者简介:江力勤,男,主任医师,教授,硕士生导师,主要从事临床心血管内科及实验工作。Tel: 0573-82054580 E-mail: jiangliqin@medmail.com.cn
基金资助:
浙江省科技厅公益性技术应用研究计划项目(2010C33008);浙江省嘉兴市科技计划项目(2010AY1036)

Experimental study on the effects of amiodarone on thyroid function and morphology in SD rats

JIANG Li-qin, WANG Zhi-gang, JI Yu-zhen

Department of Science and Education Laboratory, the Second Hospital of Jiaxing, Jiaxing, 314000, Zhejiang, China

Received:2012-02-03 Revised:2012-04-28 Online:2012-05-26 Published:2012-05-28

摘要/Abstract

摘要： 目的:探讨胺碘酮对SD大鼠甲状腺组织的激素分泌、信号蛋白表达及形态结构等影响。方法: 通过对胺碘酮低剂量组(50 mg·kg^-1·d^-1)及高剂量组(200 mg·kg^-1·d^-1)的SD大鼠14周的饲养,取静脉血测游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、总蛋白(TP)、甘油三酯(TG),取甲状腺组织观察Bcl-2蛋白的表达及Caspase-3蛋白活性高低,并进行组织学检查。结果: 用药后SD大鼠外观出现脱毛、行动迟缓、体重下降,血清总蛋白下降;FT3随胺碘酮剂量的增大而下降,FT4在低剂量组略有增高,而在高剂量组则下降;Bcl-2蛋白表达在用药组均增强,而凋亡效应因Caspase-3活性无差异。结论:胺碘酮对SD大鼠甲状腺的影响主要表现为甲状腺激素代谢受抑制,且随剂量的增大而明显,此时甲状腺组织Bcl-2蛋白表达增强,而Caspase-3细胞凋亡效应因子尚未启动。

关键词: 胺碘酮, 甲状腺, Bcl-2蛋白, Caspase-3

Abstract: AIM: To investigate the effects of amiodarone on thyroid hormone secretion, signaling protein expression and morphology.METHODS: SD rats were divided into low-dose group (50 mg·kg^-1·d^-1) and high-dose group (200 mg·kg^-1·d^-1), feeding amiodarone for 14 weeks respectively. Free triiodothyronine (FT3), free thyroxine (FT4), total protein (TP), glycerin three greases (TG) were measured from SD rats' blood. Analysis of the expression for Bcl-2 protein and the activity of Caspase-3 protein were observed from SD rats' thyroid gland, and pathology examination were performed.RESULTS:After amiodarone medication, SD rats' appearance were hair removal, sluggish, weight loss, serum total protein decreased, FT3 decreased with amiodarone's dose increasing, FT4 in the low-dose group slightly increased, while in the high-dose group decreased. The positive expression of Bcl-2 in low-dose group and high-dose group, while negative expression of Caspase-3 in all of them(P>0.05).CONCLUSION: Effects of amiodarone on SD rats' thyroid were manifested as thyroid hormone metabolism were inhibited with the dose increasing, and the expression of Bcl-2 protein were enhanced, while the apoptosis by Caspase-3 induced had not been initial.

Key words: Amiodarone, Thyroid, Bcl-2, Caspase-3

中图分类号:

R965.2

江力勤, 王志刚, 季玉珍. 胺碘酮对SD大鼠甲状腺功能及形态影响的实验研究[J]. 中国临床药理学与治疗学, 2012, 17(5): 508-512.

JIANG Li-qin, WANG Zhi-gang, JI Yu-zhen. Experimental study on the effects of amiodarone on thyroid function and morphology in SD rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(5): 508-512.

参考文献

[1] Cohen-Lehman J, Dalai P, Danzi S, et al. Effects of amiodarone therapy on thyroid function [J]. Nat Rev Endocrinol, 2010, 6(1): 34-41.
[2] DeDea L. Simvastatin dosing restrictions; monitoring amiodarone therapy [J]. JAAPA, 2011, 24(9): 16.
[3] Basaria S, Cooper DS. Amiodarone and the thyroid [J]. Am J Med, 2005, 118(7): 706-714.
[4] Han TS, Williams GR,Vanderpump MP. Benzofuran derivatives and the thyroid [J].Clin Endocrinol, 2009, 70(1): 2-13.
[5] Eskes SA, Wiersinga WM. Amiodarone and thyroid [J]. Best Pract Res Clin Endocrinol Metab, 2009, 23(6): 735-751.
[6] Kessenich CR, Higgs DA. Understanding amiodarone-induced hypothyroidism[J]. Nurse Pratt, 2010, 35(6): 14-15.
[7] Czarnywojtek A, Czepczynski R, Ruchala M, et al. Radioiodine therapy in patients with amiodarone- induced thyrotoxicosis (AIT) [J]. Neuro Endocrinol Lett, 2009, 30(2): 209-214.
[8] Wang K, Sun YN, Liu JY, et al. The impact of iodine excess on thyroid hormone biosynthesis and metabolism in rats [J]. Biol Trace Elem Res, 2009, 130(1): 72-85.
[9] Solis-S JC, Villalobos P, Orozco A, et al. Inhibition of intrathyroidal dehalogenation by iodide [J]. J Endocrinol, 2011, 208(1): 89-96.
[10] Yiu KH, Jim MH, Siu CW, et al. Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome [J]. Clin Endocrino1 Metab, 2009, 94(1): 109-114.
[11] Bogazzi F, Bartalena L,Martino E.Approach to the patient with amiodarone-induced thyrotoxicosis [J].Clin Endocrinol Metab,2010, 95(6): 2529-2535.
[12] Zhao W, Gao BL, Yi GF,et al. Apoptotic study in Graves disease treated with thyroid arterial embolization [J]. Endocrine J, 2009, 56(2): 201-211.
[13] Nadine T, Ali T, Regis C, et al. Anti-tumoral effect of a celecoxib low dose on a model of human medullary thyroid cancer in nude mice [J]. Thyroid, 2009, 19(6): 613-621.
[14] Ying H, Willingham MC, Cheng SY. The steroid receptor coactivator-3 is a tumor promoter in a mouse model of thyroid cancer [J]. Oncogene, 2008, 27(6): 823-830.
[15] 熊少伟,王玲、赵洋,等. 甲状腺癌组织中p53、Bcl-2和TPO的表达及临床意义[J].中国医药导报,2011,8(4):19-21
[16] 邓利娟,李湛军,罗楹,等. Caspase抑制剂F1013对急性肝衰竭大鼠肝细胞凋亡的影响. 中国临床药理学与治疗学,2010,15(11):1229-1233.
[17] Weidinger C, Karger S, Krause K, et al. Distinct regulation of intrinsic apoptosis in benign and malignant thyroid tumours [J]. Horm Metab Res, 2010, 42(8):553-556.