摘要
目的研究胺碘酮的剂量和性别及其交互效应对大鼠甲状腺组织功能的影响。方法雌雄各半的SD大鼠随机分为3组:对照组和低、高剂量(50,200mg·kg-1·d-1)胺碘酮实验组(均n=20),给药15周。分别于给药第4,8,12,15周末取血,检测游离T3(FT3)、游离T4(FT4)和促甲状腺激素(TSH)水平;称取甲状腺重量并计算脏器系数,同时测定甲状腺Bcl-2蛋白的表达和Caspase-3的活性,进行甲状腺病理组织检查。结果胺碘酮导致FT3水平下降,与剂量呈正相关,且在12周水平降至最低点。低剂量胺碘酮实验组的FT4水平较对照组轻度上升,而高剂量胺碘酮实验组的FT4水平均小于对照组(第4周除外)。FT3水平与性别呈正相关,与剂量呈负相关;而FT4水平与性别、剂量均无线性相关。高剂量胺碘酮实验组的Bcl-2蛋白表达均有不同程度的增加。结论胺碘酮剂量水平和性别存在交互作用,雄性更易出现甲状腺功能减退。
Objective To investigate the effect of amiodarone dosage level and gender and its interaction on thyroid function in rats .Methods Sixty SD rats, half male and half female, were randomly divided into three groups, with 20 in each group： control group, low and high dosages （50,200 mg·kg^-1·d^-1 ） amiodarone groups, administered 15 weeks. Free triiodothyronine （FT3）, free thyroxine （FT4） and thyroid stimula-ting hormone（TSH） were measured at the 4th,8th,12nd and 15th week. All the rats were sacrificed, thyroid weight, thyroid weight /body weight coefficient.The protein expression of Bcl -2 and the activity of caspase -3, optical microscope pathologic and electron microscope examination were performed.Results With regard to the control group, FT3 level decreased with the dosage of amiodarone increasing , reaching the lowest in the 12nd week.FT4 level sligltly increased in low dosage group, but was lower than control group in high dosage group other than the 4th week.Gender and dosage factors had ineractional effect on FT 3 level, gender was positively correlation with FT3 level, but had no influ-ence on FT4 level.The dosage was negatively correlation with FT3 level. The positively expression of Bcl -2 in high dosage group.The his-topathologic examination found the rupture of thyroid fossil and the enlargementof endoplasmic reticulum, cavitation and so on in low dosage and high dosage group.Conclusion The hypothyroidism was caused by amiodarone in a dosage -dependent manner. Gender and the dosage have interactional effect .Males are more likely to become hypothyroidism after amiodarone adminstration.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2014年第10期932-935,共4页
The Chinese Journal of Clinical Pharmacology
基金
浙江省科技厅公益技术应用研究计划基金资助项目(2010C33008)
浙江省嘉兴市科技计划基金资助项目(2010AY1036)
关键词
胺碘酮
性别
甲状腺功能
交互效应
amidarone
gender
thyroid function
ineractional effect
