高原环境致肠道屏障损伤的研究进展OA

The integrity of the intestinal barrier is the basis of physiological function of the intestine,which is essential for maintaining nutrient absorption,antigen exclusion,and immune homeostasis.High-altitude environments are characterized by hypobaric hypoxia and are often complicated by combined stresses such as cold,intense ultraviolet radiation,increased physical exertion,dehydration,and dietary changes.These factors may lead to synergistic dysfunction of the mechanical,chemical,immune,and biological barriers of the intestine,thereby inducing local or systemic inflammatory responses.Current evidence indicates that high-altitude-related intestinal barrier injury is not driven by a single pathway but is co-mediated by multiple factors:aberrant activation of hypoxia-inflammation signaling pathways,including hypoxia-inducible factor-1α(HIF-1α)and nuclear factor-κB(NF-κB);synergistic enhancement of Notch and Wnt/β-catenin signaling pathways leading to goblet cell reduction and insufficient mucin 2(MUC2)secretion;imbalance of T helper 17/regulatory T cells(Th17/Treg)and activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome;as well as gut microbiota dysbiosis and weakened protective effects of short-chain fatty acids(SCFAs).This article systematically reviews the molecular mechanisms underlying high-altitude-induced intestinal barrier injury,and proposes a multi-mechanism synergistic model under the"adaptation-decompensation"framework on this basis.Combined with scenarios of acute high-altitude exposure,it summarizes the evidence progress and limitations of intervention strategies of ameliorating intestinal barrier injury,aiming to provide a theoretical basis and practical reference for the prevention and intervention of high-altitude-related intestinal injury.