Medical College of Qinghai University, Xining, Qinghai, China; The Key Laboratory of Science and Technology for High Altitude Medicine, Xining, China.
Medical College of Qinghai University, Xining, Qinghai, China.
Biomed Pharmacother. 2020 Sep;129:110477. doi: 10.1016/j.biopha.2020.110477. Epub 2020 Jul 6.
The pathogenesis and mechanism of colitis may be related to intestinal flora, genetic susceptibility, environmental and immune factors. Among these various factors, the importance of environmental factors in the pathogenesis of colitis has been increasingly recognized. The purpose of this study was to investigate the effects of hypoxia on intestinal mucosal immunity.
Experimental colitis was induced by oral gavage of Citrobacter rodentium (C. rodentium) in mice, then divided into normoxia group and hypoxia group. Mice were sacrificed after 2 weeks. Physiological and blood biochemical indicators were monitored to verify the hypoxia model. The body weight, fecal bacterial output, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The percentage of CD4 IFN-γ (Th1) and CD4 IL-17 (Th17) cells in mesenteric lymph nodes (MLN) were detected by flow cytometry. The levels of mucosal antimicrobial peptides (AMPs), related inflammatory factors and transcription factors in colon tissues were detected by qRT-PCR.
Mice in hypoxic C. rodentium infection (Hypoxia + C.r.) group exhibited significant decrease in body weight, increase in fecal bacterial pathogen output, and more severe histopathological damage in the colon compared with the C. rodentium infection (Nomoxia + C.r.) group. Meanwhile, the level of NF-κB, TLR4, COX-2, IL-6 and TNF-α of colonic tissue were increased, while IL17, IL-22, and Reg3γ were decreased. The percentage of CD4 IFN-γ (Th1) and CD4 IL-17 (Th17) cells in MLN were significantly decreased in mice of Hypoxia + C.r. group, accompanied by the decreased of IFN-γ and IL-17. In addition, the level of the T-bet, RORγt, IL-12 and IL-23 were decreased in mice of Hypoxia + C.r. group.
Hypoxic exposure significantly exacerbates the symptoms and the pathological damage of mice with colitis and influences the immune function by down-regulating Th1 and Th17 responses in C. rodentium-induced colitis in mice.
结肠炎的发病机制可能与肠道菌群、遗传易感性、环境和免疫因素有关。在这些因素中，环境因素在结肠炎发病机制中的重要性日益受到重视。本研究旨在探讨缺氧对肠道黏膜免疫的影响。
采用口服柠檬酸杆菌（C. rodentium）诱导小鼠实验性结肠炎，分为常氧组和缺氧组。2 周后处死小鼠，监测生理和血液生化指标以验证缺氧模型。观察体重、粪便细菌排出量、结肠长度和结肠组织病理学变化，评估结肠炎严重程度。采用 ELISA 法检测结肠组织细胞因子浓度。采用流式细胞术检测肠系膜淋巴结（MLN）中 CD4 IFN-γ（Th1）和 CD4 IL-17（Th17）细胞的百分率。采用 qRT-PCR 法检测结肠组织中黏膜抗菌肽（AMPs）、相关炎症因子和转录因子的水平。
缺氧柠檬酸杆菌感染（Hypoxia + C.r.）组小鼠体重明显下降，粪便细菌病原体排出量增加，结肠组织学损伤较柠檬酸杆菌感染（Nomoxia + C.r.）组更为严重。同时，结肠组织 NF-κB、TLR4、COX-2、IL-6 和 TNF-α水平升高，而 IL17、IL-22 和 Reg3γ水平降低。Hypoxia + C.r.组小鼠 MLN 中 CD4 IFN-γ（Th1）和 CD4 IL-17（Th17）细胞的百分率明显降低，同时 IFN-γ和 IL-17 减少。此外，Hypoxia + C.r.组小鼠 T-bet、RORγt、IL-12 和 IL-23 水平降低。
缺氧暴露显著加重柠檬酸杆菌诱导的结肠炎小鼠的症状和病理损伤，并通过下调柠檬酸杆菌诱导的结肠炎小鼠 Th1 和 Th17 反应影响免疫功能。
