| 摘要: |
| 目的 探讨二甲双胍对甲状腺功能减退大鼠甲状腺激素水平的影响及其机制。方法 取3个月龄雄性SD大鼠36只，随机分为正常对照（NC）组、甲状腺功能减退（HT）组、二甲双胍（Met）组。HT组和Met组以含0.01%氨基三唑的饮用水喂养大鼠4周制备甲状腺功能减退大鼠模型，NC组大鼠喂养普通饮用水。造模成功后，Met组用200 mg/kg二甲双胍灌胃，HT组和NC组用等体积0.05%羟甲基纤维素钠（CMC-Na）灌胃。于灌胃第8周时对3组大鼠甲状腺组织行H-E染色，采用qPCR检测下丘脑促甲状腺激素释放激素前体（proTRH） mRNA的表达；于灌胃第8、12周时采用电化学发光法检测3组大鼠血清T3、T4水平，采用qPCR和蛋白质印迹法检测甲状腺组织钠碘同向转运体（NIS） mRNA和蛋白表达。结果 在灌胃8、12周时，HT组大鼠血清T3、T4水平均低于NC组，而Met组T3、T4水平均高于HT组（P<0.05）。灌胃8周时，H-E染色结果显示NC组滤泡大小不等，内见大量胶质及吸收空泡；HT组大鼠甲状腺滤泡缩小，滤泡上皮成柱状，滤泡周围吸收空泡减少；Met组滤泡上皮增生较HT组稍改善。灌胃8周时，qPCR结果显示HT组大鼠下丘脑proTRH和甲状腺组织NIS mRNA表达均高于NC组，而Met组均低于HT组（P<0.05）；蛋白质印迹法检测结果显示Met组NIS蛋白表达低于HT组（P<0.05），而HT组和NC组NIS蛋白表达差异无统计学意义（P>0.05）。灌胃12周时，HT组和Met组甲状腺组织NIS mRNA表达差异无统计学意义（P>0.05），Met组NIS蛋白表达高于HT组（P<0.05）。结论 二甲双胍能升高甲状腺功能减退大鼠的甲状腺激素水平，但短期内并不是由甲状腺NIS表达升高所致。 |
| 关键词: 甲状腺 二甲双胍 甲状腺激素类 甲状腺功能减退症 钠碘同向转运体 |
| DOI：10.16781/j.0258-879x.2017.05.0589 |
| 投稿时间：2016-10-24修订日期：2017-03-17 |
| 基金项目:国家重点基础研究发展计划(“973”计划,2005CB523304) |
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| Effect of metformin on thyroid hormone in rats with hypothyroidism |
| XUE Song,WANG Chao-qun,ZOU Jun-jie,LIU Zhi-min* |
(Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author) |
| Abstract: |
| Objective To explore the effect of metformin on thyroid hormone in rats with hypothyroidism and its mechanisms. Methods A total of 36 three-month-old male SD rats were randomly divided into normal control (NC) group and hypothyroidism (HT) group, metformin (Met) group. The rats in HT group and Met group was fed with 0.01% amino three triazole (AMT) water for 4 weeks to create hypothyroidism rat model, while NC group were fed with normal water. After modeling, the rats in Met group were intragastrically administrated with metformin 200 mg/kg, while the rats in HT group and NC group were intragastrically administrated with equal volume of 0.05% carboxymethylcellulose sodium (CMC-Na). After intragastric administration for eight weeks, the rats in each group were sacrificed to observe thyroid tissues with H-E staining, and to detect prothyrotropin-releasing hormone (proTRH) mRNA expression with qPCR assay. After intragastric administration for 8 and 12 weeks, serum T3 and T4 levels were detected using electrochemiluminescence assay, rat thyroid sodium/iodide symporter (NIS) mRNA and protein expressions were detected by qPCR and Western blotting, respectively. Results T3 and T4 levels of rats in HT group were significantly lower than those in NC group after 8 and 12 weeks of intragastric administration, while T3 and T4 in Met group were significantly higher than those in HT group (P<0.05). At week eight of intragastric administration, H-E staining showed that there was a greater variability in the size of folliculars, in which a large number of colloid and vacuoles were observed in the NC group; thyroid folliculars in the HT group were shrunk, the follicular epithelial tissues were columnar, and vacuoles around the follicles were decreased; and the thyroid follicular epithelial tissues hyperplasia in the Met group was slightly improved versus the HT group. At week eight of intragastric administration, the results of qPCR showed that thyroid tissue NIS mRNA and hypothalamic proTRH mRNA expressions in HT group were higher than those in NC group, while those in Met group were lower than those in HT group (P<0.05); Western blotting results showed that NIS protein expression in Met group was significantly lower than that in HT group (P<0.05), and there was no significant difference in NIS protein expression between HT group and NC group (P>0.05). After 12 weeks, there was no significant difference in NIS mRNA expression between HT group and Met group (P>0.05), while NIS protein in Met group was significantly higher than that in HT group (P<0.05). Conclusion Metformin can increase the thyroid hormone level, but its short-term mechanism may not be related to promoting the level of NIS. |
| Key words: thyroid gland metformin thyroid hormones hypothyroidism sodium iodide symporters |
