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肠系膜缺血性疾病和危重症病人的肠道血流减少、炎性激活会引起严重的肠缺血、缺氧状态。缺氧诱导因子(HIF)调控下游一系列基因转录,介导机体内源性炎性缓解机制的运行,参与肠道的适应性改变。在缺氧状态下,HIF蛋白转录后分解减少,使其能稳定存在并激活一系列下游基因参与,以缓解缺血后的肠损伤。目前受关注的有细胞内腺苷相关信号通路,尤其是A2B腺苷受体通路及缺氧诱导的神经生长因子-1介导缺血后信号通路。HIF介导的抗炎效应也参与缺血后肠功能的保护。血栓导致的肠缺血HIF还参与肠道血管的再通过程。HIF相关通路的研究为治疗肠缺氧损伤和继发多器官功能障碍提供诸多潜在靶点,针对相关靶点干预措施的研究也取得十分良好的效果,但目前还局限于细胞和转基因动物模型中。将来部分这类新型药物有可能从实验室转入临床,给肠道缺氧性疾病的治疗带来新的思路。以下将对HIF在肠缺氧中的最新研究作一综述。
Mesenteric ischemic disease and critically ill intestinal blood flow, inflammatory activation can cause severe intestinal ischemia, hypoxia. Hypoxia-inducible factor (HIF) regulates the transcription of a series of downstream genes, mediates the operation of the endogenous inflammatory mediation mechanism, and participates in the adaptive changes of the intestine. Under hypoxia, HIF protein is reduced after transcription, which makes it stably exist and activates a series of downstream genes to alleviate intestinal damage after ischemia. At present, there are intracellular adenosine related signaling pathways, especially A2B adenosine receptor pathway and hypoxia-inducible nerve growth factor-1-mediated signaling pathway after ischemia. HIF-mediated anti-inflammatory effects are also involved in the protection of ischemic intestinal function. Hypothyroidism caused by intestinal ischemia HIF is also involved in the process of intestinal vascular recanalization. HIF-related pathways provide many potential targets for the treatment of intestinal hypoxia injury and secondary multiple organ dysfunction. Studies on interventions targeting these targets have also achieved very good results, but are still limited to cell and transgenic animal models . Some of these new drugs in the future may be transferred from the laboratory clinical, to the intestinal hypoxia disease treatment brings new ideas. The following will be HIP in intestinal hypoxia in the latest research are reviewed.