Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, PR CHINA.
Med Sci Sports Exerc. 2020 Aug;52(8):1710-1718. doi: 10.1249/MSS.0000000000002298.
This study was to investigate the mechanism of intestinal physical and immune barriers in the occurrence of high-intensive exercise-induced gastrointestinal symptoms.
An overtraining model of male C57BL/6 mice was established by running-to-exhaustive exercise. Then, the mice were sacrificed, and a series of evaluation indicators, including the routine blood analysis as well as histological examinations, inflammatory factors, ultrastructure observation, and intestinal permeability of the gut, were measured based on this model. The expressions of inflammatory factors tumor necrosis factor α, interferon-γ, and interleukin (IL)-6 as well as the tight junction and adherence junction proteins ZO-1, Occludin, Claudin-1, and E-cadherin were measured, respectively. Furthermore, the mRNA level of IL-22 and the proportion of ILC3 and IL-22 produced in CD4 T cells in lamina propria lymphocytes (LPL) were analyzed by flow cytometry. Besides, the liver glycogen and the expressions of sirtuins-3 and hypoxia-inducible factor-1a, which were associated with the intestinal metabolism phenotype, were analyzed by Western blotting.
Exhaustive exercise induced a disrupted intestinal barrier integrity, an aggravated intestinal inflammation, increased gut permeability, and the reduced IL-22 mRNA level. Compared with the nonexercise mice, the IL-22 produced in LPL was reduced followed by exhaustive exercise, whereas the proportion of IL-22 produced in CD4 T cells was still unchanged. Significantly, the proportion of ILC3 in the LPL was decreased obviously, including the NCR ILC3. Furthermore, the intestinal metabolism phenotype assessment showed lower liver glycogen and blood glucose as well as higher blood lactic acid and hypoxia-inducible factor-1a, respectively.
The data indicated that the acute high-intensity running-induced gastrointestinal symptom is closely associated with a reduced percentage of ILC3 and IL-22 level in the LPL, possibly due to the glycogen exhaustion and intestinal mucosa hypoperfusion.
本研究旨在探讨高强度运动引起胃肠道症状的肠道物理和免疫屏障机制。
通过跑至力竭运动建立雄性 C57BL/6 小鼠的过度训练模型。然后，在该模型基础上，通过牺牲小鼠并测量一系列评估指标，包括常规血液分析和组织学检查、炎症因子、超微结构观察和肠道通透性，来测量肠道。分别测量炎症因子肿瘤坏死因子-α、干扰素-γ和白细胞介素（IL）-6 以及紧密连接和粘附连接蛋白 ZO-1、Occludin、Claudin-1 和 E-钙粘蛋白的表达。此外，通过流式细胞术分析固有层淋巴细胞（LPL）中 IL-22 的 mRNA 水平和 CD4 T 细胞中产生的 ILC3 和 IL-22 的比例。此外，通过 Western blot 分析与肠道代谢表型相关的肝糖原和沉默调节蛋白-3 和缺氧诱导因子-1a 的表达。
力竭运动导致肠道屏障完整性受损、肠道炎症加重、肠道通透性增加和 IL-22 mRNA 水平降低。与不运动的小鼠相比，运动后 LPL 中产生的 IL-22 减少，而 CD4 T 细胞中产生的 IL-22 比例仍保持不变。值得注意的是，LPL 中 NCR ILC3 的数量明显减少。此外，肠道代谢表型评估显示肝糖原和血糖降低，血乳酸和缺氧诱导因子-1a 升高。
数据表明，急性高强度跑步引起的胃肠道症状与 LPL 中 ILC3 和 IL-22 水平的百分比降低密切相关，可能是由于糖原耗竭和肠道黏膜低灌注所致。
