实验动物与比较医学 ›› 2021, Vol. 41 ›› Issue (3): 232-237.DOI: 10.12300/j.issn.1674-5817.2020.153

• 论著:人类疾病动物模型 • 上一篇    下一篇

慢性间歇性低氧模型大鼠的甲状腺功能分析

田慧1, 高隆2, 王泽辉3   

  1. 1.榆林市第一医院内分泌科,绥德 718000;
    2.榆林市第一医院呼吸内科,榆林 719000;
    3.延安大学医学院基础医学院,延安 716000
  • 收稿日期:2020-12-22 修回日期:2020-12-22 出版日期:2021-06-25 发布日期:2021-07-05
  • 作者简介:田 慧(1983—), 女, 主治医师, 主要从事内分泌疾病的诊治及相关研究。E-mail: zl336787@163.com
  • 基金资助:
    陕西省重点研发计划(2019SF-14213)

Thyroid Function of Chronic Intermittent Hypoxia Rat Model

TIAN Hui1, GAO Long2, WANG Zehui3   

  1. 1. Department of Endocrinology, Yulin First Hospital, Suide 718000, China;
    2. Department of Respiratory Medicine, First Hospital of Yulin City, Yulin 719000, China;
    3. School of Basic Medicine, Yan'an University School of Medicine, Yan'an 716000, China
  • Received:2020-12-22 Revised:2020-12-22 Online:2021-06-25 Published:2021-07-05

摘要: 目的 通过慢性间歇性低氧(chronic intermittent hypoxia,CIH)大鼠模型探索阻塞性睡眠呼吸暂停低通气综合征与甲状腺功能的关系。方法 SD大鼠分为对照(control)组、CIH组和复氧(reoxygenation,RH)组,利用低氧舱建立CIH动物模型,并对CIH模型进行鉴定;放射免疫检测各组大鼠血清中促甲状腺激素释放激素(thyrotropin releasing hormone,TRH)、促甲状腺激素(thyroid stimulating hormone,TSH)、三碘甲状腺原氨酸(triiodothyronine,T3)和甲状腺素(thyroxine,T4)的表达水平;HE染色和甲苯胺蓝染色观察各组大鼠甲状腺组织的病理变化;电子显微镜观察各组大鼠甲状腺组织超微结构的变化。结果 CIH组和RH组大鼠的血氧饱和度为70%~92%,动脉氧分压为60.7~80.1 mmHg,接近阻塞性睡眠呼吸暂停低通气综合征的病理生理特点,因此CIH动物模型建立成功。与control组比较,CIH组大鼠血清中TRH、TSH、T3和T4的表达水平明显降低(均P<0.05),甲状腺质量明显增加(P<0.01);与CIH组比较,RH组大鼠血清中TRH、TSH、T3和T4的表达水平明显增加(均P<0.05),甲状腺质量减少(P<0.05)。HE染色和甲苯胺蓝染色显示,control组大鼠甲状腺组织有完整的甲状腺滤泡;CIH组大鼠甲状腺的正常滤泡结构丧失,一些滤泡细胞显示空泡,基核较暗;RH组大鼠甲状腺组织显示正常的滤泡结构,但是某些滤泡细胞仍呈空泡状,带有深色核。电子显微镜观察发现,control组大鼠的甲状腺具有正常的滤泡细胞;CIH组大鼠甲状腺滤泡细胞的细胞核收缩,异染色质增加,基质损失;RH组大鼠的甲状腺部分有完整的滤泡细胞结构。结论 CIH可导致大鼠甲状腺功能调节紊乱,恢复吸氧可使甲状腺功能部分恢复正常。

关键词: 阻塞性睡眠呼吸暂停低通气综合征, 慢性间歇性缺氧, 甲状腺功能, 大鼠

Abstract: Objective To establish a chronic intermittent hypoxia (CIH) rat model to explore the correlation of obstructive sleep apnea-hypopnea syndrome (OSAHS) with thyroid function and its mechanism. Methods SD rats were divided into control group, CIH group, and reoxygenation group (RH group). The CIH animal model was established using a hypoxic chamber and was identified. The expression levels of thyroid stimulating hormone (TRH), thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) in the serum of each group of rats were detected by radioimmunoassay. The pathological changes in the thyroid tissue in each group were observed by hematoxylin and eosin (HE) staining and toluidine blue staining. Changes in the ultrastructure of the thyroid tissue in rats were observed by electron microscopy. Results The CIH and RH rats had blood oxygen saturations of 70%-92%, and arterial oxygen partial pressures of 60.7-80.1 mmHg, which were close to the pathophysiology of OSAHS, therefore, the CIH animal model was successfully established. Compared with the expression levels of TRH, TSH, T3, and T4 in the serum of rats in the control group, those of rats in the CIH group were significantly reduced (all P < 0.05), while the thyroid mass was significantly increased (P < 0.01). Compared with the expression levels of TRH, TSH, T3, and T4 in the serum of the CIH group rats, those in the serum of the RH group rats increased significantly (all P < 0.05), while the thyroid mass was decreased (P < 0.05). The HE and toluidine blue staining results showed that the thyroid tissue of the control group had intact thyroid follicles, whereas the thyroid tissue of the CIH group showed normal follicular structure loss, some follicular cells with vacuoles, and a dark basal nucleus. The thyroid tissue of the RH group showed normal follicular structure, but some follicular cells were still vacuolar with dark nuclei. Electron microscopy showed that the thyroid tissue of the control group rats had normal follicular cells, while the follicular cells in the thyroid tissue of the CIH group showed nuclear contraction, increased heterochromatin, and matrix loss. The thyroid tissue of the RH group had complete follicular cell structure. Conclusion CIH can cause thyroid dysregulation in rats, and thyroid function partially returns to normal once hypoxia is resolved.

Key words: Obstructive sleep apnea-hypopnea syndrome, Chronic intermittent hypoxia, Thyroid function, Rats

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