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褪黑素对大鼠下丘脑-垂体-甲状腺轴相关激素及组织超微结构的影响
宝轶,卜乐,邹俊杰,石勇铨,刘志民*
0
(第二军医大学长征医院内分泌科,上海 200003)
摘要:
目的:观察褪黑素(melatonin,Mel)对大鼠下丘脑-垂体-甲状腺轴相关激素分泌及分泌轴器官超微结构的影响。方法:SD雄性大鼠随机分为4组(n=15):正常对照组、低剂量Mel干预组(0.5 mg·kg-1·d-1)、中剂量Mel干预组(10 mg·kg-1·d-1)、高剂量Mel干预组(50 mg·kg-1·d-1)。Mel干预组每日腹腔注射不同剂量Mel,各组分别于干预后第1、2、3周处死5只大鼠,留取血清及下丘脑、垂体、甲状腺组织。放射免疫分析法检测血清T3、T4、FT3、FT4、促甲状腺激素(TSH)水平,实时荧光定量PCR(RT-PCR)检测下丘脑proTRH mRNA表达水平,电镜观察下丘脑、垂体、甲状腺超微结构的变化。结果:药物干预后第1、2、3周,中、高剂量Mel干预组血清T4、FT3、FT4、TSH水平明显低于对照组及低剂量Mel干预组(P<0.01);中、高剂量Mel干预组血清T4水平逐周降低(P<0.01);Mel干预2周后TSH水平下降,第3周与前2周相比差异有统计学意义(P<0.01)。Mel干预后第1、2、3周,高剂量Mel组proTRH mRNA表达水平低于正常对照组(P<0.01),并随给药时间的延长,proTRH mRNA表达水平呈先降低后升高的趋势;下丘脑、垂体、甲状腺组织超微结构无明显变化。结论:中、高剂量褪黑素抑制下丘脑-垂体-甲状腺轴相关激素分泌,但对各组织超微结构影响不大。
关键词:  褪黑素  下丘脑-垂体-甲状腺轴  激素  超微结构
DOI:10.3724/SP.J.1008.2009.01009
投稿时间:2009-03-12修订日期:2009-04-29
基金项目:国家重点基础研究规划(“973”计划,2005CB523304).
Effect of melatonin on hormone secretion and tissue ultrastructure of hypothalamus-pituitary-thyroid axis in rats
BAO Yi,BU Le,ZOU Jun-jie,SHI Yong-quan,LIU Zhi-min*
(Department of Endocrinology,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China)
Abstract:
Objective:To investigate the effect of melatonin(Mel) on hormone secretion and tissue ultrastructure of hypothalamus-pituitary-thyroid axis(HPTA) in rats.Methods: A total of 60 male Sprague-Dawley rats were evenly randomized into four groups: control, low-dose Mel(0.5 mg·kg-1·d-1),middle-dose Mel(10 mg·kg-1·d-1),and high-dose Mel(50 mg·kg-1·d-1 ) group.The rats in the latter 3 groups received intraperitoneal injection of different doses of Mel daily.At 1st,2nd and 3rd weeks after treatment,rats were sacrificed and blood serum samples,hypothalamus,pituitary and thyroid tissues were obtained.Serum T3,T4,FT3,FT4 and TSH levels were estimated by radioimmunoassay (RIA).Expression of proTRH mRNA in hypothalamus tissues were detected by real time RT-PCR.The ultrastructures of hypothalamus,pituitary and thyroid were observed under transmission electronic microscope.Results: The serum levels of T4,FT3,FT4 and TSH in the middle-dose and high-dose Mel groups were significantly decreased compared with those in the control and low-dose Mel group at 1st ,2nd and 3rd weeks(P<0.01).T4 levels decreased in the middle-dose and high-dose Mel groups at a weekly basis,with significant difference found between different weeks (P<0.01).TSH level was deceased at the 2nd week, and that at the 3rd week was significantly lower than those at the first two weeks (P<0.01).The expression of proTRH mRNA was lower in high-dose Mel group compared to that in the control group at 1st ,2nd and 3rd weeks.With the prolongation of Mel treatment,expression of proTRH mRNA had a decreasing tendency first and an increasing tendency later.No obvious pathological ultrastructure changes were found in the hypothalamus,pituitary and thyroid tissues.Conclusion: Melatonin may inhibit Hypothalamus-Pituitary-Thyroid axis in a time- and dose-dependent manner in rats.
Key words:  melatonin  hypothalamus-pituitary-thyroid axis  hormone  ultrastructure