Exercise induces tissue hypoxia and HIF-1 alpha redistribution in the small intestine
Exercise induces tissue hypoxia and HIF-1 alpha redistribution in the small intestine
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运动导致小肠组织缺氧和 HIF-1 α 重新分布
DOI：
10.1016/j.jshs.2019.05.002
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发表时间：
2020
影响因子：
11.7
通讯作者：
Chen Peijie
中科院分区：
文献类型：
--
作者：
Wu Die;Cao Wei;Xiang Dao;Hu Yi-Ping;Luo Beibei;Chen Peijie
背景运动会导致组织之间的血流重新分配，导致内脏灌注不足。肠上皮细胞位于厌氧腔和具有氧梯度的高代谢固有层之间。缺氧诱导因子(HIF)-1α在氧通量转录反应中起关键作用。方法本研究采用盐酸哌莫硝唑染色观察不同器官的组织缺氧情况,其可能受到血流重新分配的影响。采用HIF-1α荧光素酶报告基因ROSA26氧依赖性降解结构域（ODD）-Luc/+小鼠模型（ODD结构域-Luc；雌性，n=3~6/组）检测肠道中HIF-1α的表达。我们采用了3种游泳模型：中度运动30分钟，负重5%体重的大强度运动1.5小时，长时间运动3小时。结果我们发现，1次不同强度的游泳可以引起小肠、结肠、肝脏和肾脏中的组织缺氧重新分布，但不会引起脾脏、心脏和骨骼肌中的组织缺氧重新分布。我们的数据显示，运动加剧了小肠生理性缺氧的程度。接下来，使用 ODD-Luc 小鼠，我们发现适度的运动会增加体内小肠中的 HIF-1α 水平。运动后HIF-1α水平随时间逐渐下降。有趣的是，组织缺氧的重新分布和HIF-1α表达的增加与运动强度和持续时间无关。结论本研究提供了证据表明小肠是运动引起的组织缺氧和HIF-1α重新分布的主要靶器官，提示HIF-1α可能是运动后调节胃肠功能的潜在靶点。
BackgroundExercise induces blood flow redistribution among tissues, leading to splanchnic hypoperfusion. Intestinal epithelial cells are positioned between the anaerobic lumen and the highly metabolic lamina propria with an oxygen gradient. Hypoxia-inducible factor (HIF)-1α is pivotal in the transcriptional response to the oxygen flux.MethodsIn this study, the pimonidazole hydrochloride staining was applied to observe the tissue hypoxia in different organs, which might be affected by the blood flow redistribution. The HIF-1α luciferase reporter ROSA26 oxygen-dependent degradation domain (ODD)-Luc/+mouse model (ODD domain-Luc; female,n= 3–6/group) was used to detect the HIF-1α expression in the intestine. We used 3 swimming models: moderate exercise for 30 min, heavy-intensity exercise bearing 5% bodyweight for 1.5 h, and long-time exercise for 3 h.ResultsWe found that 1 session of swimming at different intensities could induce tissue hypoxia redistribution in the small intestine, colon, liver and kidney, but not in the spleen, heart, and skeletal muscle. Our data showed that exercise exacerbated the extent of physiological hypoxia in the small intestine. Next, using ODD-Luc mice, we found that moderate exercise increased thein vivoHIF-1α level in the small intestine. The post-exercise HIF-1α level was gradually decreased in a time-dependent manner. Interestingly, the redistribution of tissue hypoxia and the increase of HIF-1α expression were not related to the exercise intensity and duration.ConclusionThis study provided evidence that the small intestine is the primary target organ for exercise-induced tissue hypoxia and HIF-1α redistribution, suggesting that HIF-1α may be a potential target for the regulation of gastrointestinal functions after exercise.