低压低氧致小鼠胃肠应激损伤的研究  

Preliminary study on gastrointestinal stress injury induced by hypobaric hypoxia in mice

作　　者：魏雪 尚慧莹 叶岸平 肖成荣 高月 马增春[1,2] WEI Xue;SHANG Hui-ying;YE An-ping;XIAO Cheng-rong;GAO Yue;MA Zeng-chun(Guangdong Pharmaceutical University,Guangzhou 510006,China;Institute of Radiation Medicine,Academy of Military Medicine,Academy of Military Sciences,Beijing 100850,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]广东药科大学,广东广州510006 [2]军事科学院军事医学研究院辐射医学研究所,北京100850 [3]天津中医药大学,天津301617 [4]江西中医药大学,江西南昌330004

出　　处：《中国药理学通报》2024年第8期1482-1488,共7页Chinese Pharmacological Bulletin

基　　金：中医药服务能力培育与提升专项计划重点项目(No.2021ZY009)。

摘　　要：目的通过低压氧舱模拟高原缺氧环境,探究缺氧不同时间对小鼠胃肠应激损伤的影响。方法根据低压低氧不同时间设置正常对照组、低压低氧1、3、5天模型组,低压低氧处理完成后检测小肠推进率、内脏敏感性变化及胃肠道病理损伤程度;酶联免疫吸附法(ELISA)检测胃肠道IL-1β、IL-6、TNF-α含量变化,肠组织胃肠激素及肠黏膜损伤标志物二胺氧化酶、D-乳酸含量变化;Western blot实验检测肠组织紧密连接蛋白及紧密连接损伤通路相关蛋白表达变化。结果与对照组相比,模型组小鼠小肠推进率加快,肠道敏感性升高;肠黏膜损伤标志物表达升高;肠组织抑制胃肠蠕动激素降低,促胃肠蠕动激素升高;紧密连接蛋白ZO-1、claudin-1、occludin及紧密连接损伤相关通路蛋白VASP表达降低,紧密连接损伤相关通路中的NF-κB、HIF-1α、VEGF表达升高;胃肠组织IL-1β、IL-6、TNF-α表达升高;胃组织胃蛋白酶含量升高;胃肠组织1天组损伤较轻,3天、5天组损伤较重;结论在低氧低氧环境中不同时间小鼠胃肠发生应激损伤,暴露3天时胃肠功能损伤较为严重,其中肠损伤机制可能与NF-κB/HIF-1α/VEGF/VASP信号通路被激活有关。Aim To study the effects of different periods of hypoxia on gastrointestinal stress in mice by simulating hypoxia environment at high altitude in a low-pressure oxygen chamber.Methods The normal control group and the model group for 1,3 and 5 days were set up according to different periods of hypobaric hypoxia.The intestinal propulsion rate,visceral sensitivity and pathological damage of gastrointestinal tract were detected after hypobaric hypoxia treatment.The contents of IL-1β,IL-6 and TNF-αin gastrointestinal tract and the contents of gastrointestinal hormone,diamine oxidase and D-lactic acid were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of tight-junction protein and tight junction injury pathway protein in intestinal tissues were detected by Western blot.Results Compared with the control group,the intestinal propulsion rate of the model group was accelerated,and the intestinal sensitivity increased.The expression of intestinal mucosal injury markers increased.Gastrointestinal motility inhibiting hormone decreased and gastrointestinal motility promoting hormone increased.The expression of tight junction proteins ZO-1,claudin-1,occludin and VASP of tight junction injury-related pathway decreased,while the expression of NF-κB,HIF-1αand VEGF in tight junction injury-related pathway increased.The expressions of IL-1β,IL-6 and TNF-αin gastrointestinal tissue increased.The content of pepsin in gastric tissue increased.The injury of gastrointestinal tissue was less in the 1-day group,and more serious in the 3-day and 5-day groups.Conclusions Stress injury occurs in the gastrointestinal tract of mice at different time points in hypoxia and hypoxia environment,and the gastrointestinal function injury is more serious after three days of exposure,which may be related to the activation of NF-κB/HIF-1α/VEGF/VASP pathway.

关 键 词：低压低氧 小鼠 胃肠应激 小肠推进率 肠黏膜损伤 紧密连接 

分 类 号：R-332[医药卫生] R322.4R339.54R442.9R845.22