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中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (5): 432-437.doi: 10.12047/j.cjap.5898.2020.092

• 研究论文 • 上一篇    下一篇

模拟海拔5 500 m低压低氧环境对大鼠HPT轴和肠道菌群的影响*

谢亚磊, 梅颂, 熊艳蕾, 刘诗颖, 徐成丽   

  1. 中国医学科学院基础医学研究所/北京协和医学院基础学院, 北京 100005
  • 收稿日期:2019-12-02 修回日期:2020-06-29 发布日期:2021-02-25
  • 通讯作者: Tel: 010-69156924; E-mail: xuchengli@pumc.edu.cn
  • 基金资助:
    *中国医学科学院医学与健康科技创新工程项目资助(2016-I2M-1-005)

Effects of simulated 5 500 m hypobaric and hypoxia on HPT axis and intestinal flora in rats

XIE Ya-lei, MEI Song, XIONG Yan-lei, LIU Shi-ying, XU Cheng-li   

  1. Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
  • Received:2019-12-02 Revised:2020-06-29 Published:2021-02-25

摘要: 目的: 探究模拟海拔5 500 m低压低氧环境对大鼠下丘脑-垂体-甲状腺(HPT)轴和肠道菌群的影响及两者间关联。方法: 采用低压低氧舱模拟海拔5 500 m高度,构建成年雄性SD大鼠低氧模型,设置1、3、7、14、21和28 d低氧组和常氧组,并设置1 d和3 d低氧后常氧恢复组(每组大鼠8只,低氧时间为每天24 h)。记录大鼠每日体重和平均摄食量,采用16 s rDNA测序分析肠道菌群、ELISA检测血清HPT轴激素水平,进行肠道菌群与HPT轴激素相关性分析。结果: 与常氧组相比,低氧组大鼠体重和摄食量显著降低(P<0.01)。1 d、3 d低氧组大鼠血清促甲状腺素释放激素(TRH)和促甲状腺激素(TSH)水平较常氧组显著降低(P<0.05),血清总甲状腺素(TT4)、总三碘甲状腺原氨酸(TT3)、游离甲状腺素(FT4)和游离三碘甲状腺原氨酸(FT3)水平较常氧组显著增加(P<0.05)。1和3 d低氧组大鼠肠道副拟杆菌属(Parabacteroides)、乳酸杆菌属(Lactobacillus)、丁酸球菌属(Butyricimonas)、拟杆菌属(Bacteroides)、臭味杆菌属(Odoribacter)和RC4-4菌属丰度较常氧组显著增加(P<0.05),普氏菌属(Prevotella)丰度较常氧组显著降低(P<0.05)。14、21和28 d低氧组大鼠副拟杆菌属、球毛菌属(Sphaerochaeta)、阿克曼氏菌属(Akkermansia)、迷踪菌属(Elusimicrobium)丰度较常氧组显著增加(P<0.05),乳酸杆菌属、萨特氏菌属(Sutterella)丰度较常氧组显著降低(P<0.05)。肠道菌群与HPT轴激素相关性分析表明,丁酸球菌属、迷踪菌属、萨特氏菌属与TRH、TSH显著负相关(P<0.05),普氏菌属、拟杆菌属、臭味杆菌属、副拟杆菌属分别与TSH、TT4、TT3、FT4显著相关(P<0.05),乳酸杆菌属与TRH、 TSH、FT4显著相关(P<0.05),阿克曼氏菌属与TRH、FT4显著相关(P< 0.05),RC4-4菌属与TSH、TT3显著相关(P<0.05)。结论: 模拟海拔5 500 m低氧应激显著改变SD大鼠肠道菌群的构成,这可能是甲状腺功能与低氧环境相适应的变化,变化程度与低氧应激时间有关;低氧环境下大鼠肠道菌群的变化与HPT轴激素水平显著相关。

关键词: 低氧, 应激, 下丘脑-垂体-甲状腺(HPT)轴, 甲状腺激素, 肠道菌群, 大鼠

Abstract: Objective: To investigate the effects of simulated hypoxia environment at an altitude of 5 500 meters on hypothalamic-pituitary-thyroid (HPT) axis and intestinal flora of rats and the correlation between them. Methods: The hypoxia model of adult male SD rats was established by hypobaric chamber with simulated altitude of 5 500 m. The hypoxia groups were set for 1, 3, 7, 14, 21 and 28 days, and the normoxic recovery group were set for 1 and 3 days after hypoxia (8 rats per group, hypoxia time 24h per day). Daily body weight and food intake of rats were recorded. The serum levels of HPT axis hormones were detected by enzyme-linked immunosorbent assay (ELISA). Intestinal flora was analyzed by 16s rDNA sequencing. The correlation between intestinal flora and serum HPT axis hormone was analyzed by Spearman correlation analysis. Results: Compared with the normoxic group, the body weight and food intake were significantly reduced (P<0.01). In the 1-day and 3-day groups, the levels of thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) were decreased significantly (P<0.05), the levels of total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4) and free triiodothyronine (FT3) were increased significantly (P<0.05), and the abundance of Prevotella was decreased significantly (P<0.05), while those of Parabacteroides, Lactobacillus, Butyricimonas, Bacteroides, Odoribacter and RC4-4 were increased significantly (P<0.05). In the 14-day, 21-day and 28-day hypoxia groups, the levels of TRH and TSH were decreased significantly (P<0.05), and the levels of TT4 and TT3 were increased significantly (P<0.05), and there was no significant difference in other indexes, the abundance of Parabacteroides, Sphaerochaeta, Akkermansia, Elusimicrobium was increased significantly, but that of Lactobacillus and Sutterella was decreased significantly (P<0.05). Correlation analysis of intestinal flora and HPT axis hormones showed that Butyricimonas, Elusimicrobium and Sutterella were significantly negatively correlated with TRH and TSH (P< 0.05), Prevotella, Bacteroides, Odoribacter and Parabacteroides were significantly correlated with TSH, TT4, TT3 and FT4 (P< 0.05), respectively. Lactobacillus was significantly correlated with TRH, TSH and FT4 (P<0.05). Akkermansia was significantly correlated with TRH and FT4 (P<0.05). RC4-4 was significantly associated with TSH and TT3 (P<0.05). Conclusion: Hypoxia stress at an altitude simulating 5500 meters significantly changed the composition of the intestinal flora of SD rats. This may be a change in thyroid function adapted to the hypoxia environment, and the degree of change is related to the time of hypoxia stress. The change of intestinal microflora is significantly correlated with the hormone level of HPT axis.

Key words: hypoxia, stress, hypothalamus-pituitary-thyroid (HPT) axis, thyroid hormone, intestinal flora, rat

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