| 秦鹏蕊,王迦南,刘诗颖,王 茜,柴佳敏,宋巧玥,徐成丽.模拟海拔5000 m低氧环境对小鼠肠道免疫和肠道菌群的影响[J].,2022,(8):1401-1407 |
| 模拟海拔5000 m低氧环境对小鼠肠道免疫和肠道菌群的影响 |
| Effects of Simulated Hypoxic Environment at 5000 m Altitude on Intestinal Immunity and Gut Microbiota in Mice |
| 投稿时间：2021-11-24 修订日期：2021-12-20 |
| DOI：10.13241/j.cnki.pmb.2022.08.001 |
| 中文关键词: 低氧 小鼠 肠道菌群 Occludin IL-6 |
| 英文关键词: Hypoxia Mice Gut microbiota Occludin IL-6 |
| 基金项目:中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-005) |
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| 中文摘要: |
| 摘要 目的：研究模拟海拔5000 m低压低氧环境下，不同低氧暴露时间对小鼠肠道组织结构、免疫因子和肠道菌群的影响。方法：采用低压低氧舱模拟海拔5000 m高度，构建8周龄雄性C57BL/6小鼠低氧模型，随机分为1、3、5、7、14和30 d低氧组及其常氧对照组，每组6只常规饲养，记录体重。在对应时间点取材，HE染色制作小鼠回肠组织切片、免疫组织化学染色分析小鼠肠道紧密连接occludin蛋白表达，ELISA检测小鼠血浆免疫因子IL-6、IL-22和TNF-α水平，16S rDNA测序分析肠道菌群变化。结果：与常氧对照组相比，各低氧组小鼠体重均显著降低（P<0.05）。小鼠回肠组织HE 染色及免疫组化染色显示，各低氧组均出现不同程度的肠上皮绒毛缺损，淋巴细胞增多等变化，且7、14 d组低氧组小鼠紧密连接occludin蛋白表达量显著降低（P<0.05）。与常氧组相比，7 d低氧组小鼠血浆IL-6水平显著降低（P<0.05），14 d低氧组小鼠血浆IL-6水平显著增加（P<0.05）；与相应的常氧组对比，低氧组TNF-α和IL-22的水平没有显著差异，但在各低氧组间出现差异。不同低氧时间组与其常氧对照组的肠道菌群构成具有显著差异；在菌属水平上，低氧组中普雷沃菌属（Prevotella）、阿克曼氏菌属（Akkermansia）、颤螺菌属（Oscillospira）、拟杆菌属（Bacteroides）、脱硫弧菌属（Desulfovibrio）和臭气杆菌属（Odoribacter），相对丰度较高且具有显著性差异（P<0.05）；血浆免疫因子与肠道菌群相关分析表明，乳酸杆菌属（Lactobacillus）与IL-6、IL-22水平呈显著正相关（r=0.27，P<0.05；r=0.27，P<0.05）。结论：模拟海拔5000 m低压低氧环境显著改变C57BL/6小鼠肠道组织结构及其屏障功能和肠道菌群组成，肠道菌群的变化与免疫因子水平显著相关，这些变化与低氧暴露时间相关，是小鼠低氧应激响应肠道功能的适应性变化。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of simulated hypobaric hypoxic environment at 5000 m altitude on intestinal tissue structure, immune factors, and gut microbiota in mice with different hypoxia exposure times. Methods: 72 male C57BL/6 mice were divided into hypoxia groups and control groups. The hypoxia model was established by hypobaric chamber with simulated altitude of 5000 m. The hypoxia groups were set for 1, 3, 5, 7, 14, and 30 days (6 mice per group, hypoxia time 24 h per day), body weight of mice was recorded. The histopathological sections of ileum were made by HE staining. The expression levels of occludin, an intestinal tight junction protein, were analyzed by immunohistochemical staining. The levels of IL-6, IL-22, and TNF-α in plasma were detected by enzyme-linked immunosorbent assay(ELISA). Gut microbiota was analyzed by 16 s rDNA sequencing. Results: Compared with that in the control group, the body weight of hypoxia groups reduced significantly(P<0.05). HE staining and immunohistochemical staining of hypoxia groups showed that there were injury in intestinal epithelial villi and the lymphocytes increased. The expression of occludin protein decreased significantly(P<0.05) in 7- and 14-day hypoxia groups. IL-6 in plasma decreased significantly(P<0.05) in 7-day hypoxia groups and then increased significantly(P<0.05) in 14-day hypoxia groups. The characteristics of the intestinal microbial community of mice in different hypoxia exposure groups and control groups significantly changed. At genus level, the abundance of Prevotella, Akkermansia, Oscillospira, Bacteroides, Desulfovibrio, Odoribacter were significantly increased (P<0.05) in hypoxia groups. Correlation analysis of immune factors and gut microbiota showed that Lactobacillus is significantly positively correlated with IL-6 and IL-22 (r=0.27, P<0.05; r=0.27, P<0.05). Conclusion: Hypoxia stress at an altitude simulating 5000 m significantly changed the intestinal epithelium structure and barrier function and the composition of gut microbiota of mice. Changes in gut microbiota were significantly correlated with the levels of immune factor in plasma. These changes may be the adaptive response to the hypoxia environment and are related to the time of hypoxia stress. |
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