Xue ShengLong, Shi Tian, Liu Weidong, Feng Yan, Tuerxuntayi Ailifeire, Li Na, Gao Feng
College of Life Science and Technology Xinjiang University Urumqi China.
Department of Gastroenterology People's Hospital of Xinjiang Uygur Autonomous Region Urumqi China.
Food Sci Nutr. 2025 May 20;13(5):e70228. doi: 10.1002/fsn3.70228. eCollection 2025 May.
The plateau hypoxic environment is a main habitat for human beings, which can result in dysbiosis of the intestinal flora. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used anti-inflammatory drugs that can cause intestinal damage with long-term administration. Moreover, the administration of these drugs in the hypoxic plateau environment may exacerbate intestinal damage. This study aimed to investigate the therapeutic effect of resveratrol (RSV) on the intestinal injury induced by NSAIDs in rats under plateau hypoxia. Aspirin was used as the inducer to induce intestinal injury in rats. Rats were divided into seven groups: Ck (vehicle group), HCk (high-altitude control group), PAsp (plain aspirin-treated group), HAsp (High-altitude aspirin-treated group), RSVL (low-dose resveratrol-treated group), RSVM (medium-dose resveratrol-treated group), and RSVH (high-dose resveratrol-treated group). The body weight of the rats was recorded every 7 days during the experiment. On the last day of the experiment, jejunal tissues of the rats were collected for hematoxylin and eosin staining (H&E), and feces of the rats were collected for analysis of intestinal flora and metabolite analysis. The results demonstrated that RSV inhibited weight loss and intestinal damage initiated by aspirin administration in a hypoxic plateau environment. Moreover, it markedly elevated the expression levels of interleukin (IL)-10 and superoxide dismutase (SOD) while substantially reducing the expression levels of TNF-α, IL-1β, and myeloperoxidase (MPO). Furthermore, 16SrRNA gene sequence analysis showed that both aspirin and RSV altered the composition and structure of rat gut microbiomes. Metabolomics results showed that RSV altered the intestinal metabolites of aspirin-induced intestinal injury in rats, reducing the content of 2-hydroxy-3- (4-hydroxyphenyl) protonic acid and 3- [(1-carboxyvinyl) oxy] benzoate and increasing the content of coumaryl, 3-amino-4 hydroxybenzoate, and L-carnitine. Resveratrol can alleviate NSAID (Aspirin)-induced intestinal damage in the hypoxic environment of the plateau by regulating intestinal flora and metabolites, with the best effect in the RSVM group (50 mg/kg).
高原缺氧环境是人类的主要栖息地之一，可导致肠道菌群失调。非甾体类抗炎药（NSAIDs）是广泛使用的抗炎药物，长期服用可导致肠道损伤。此外，在缺氧的高原环境中使用这些药物可能会加剧肠道损伤。本研究旨在探讨白藜芦醇（RSV）对高原缺氧环境下NSAIDs诱导的大鼠肠道损伤的治疗作用。以阿司匹林作为诱导剂诱导大鼠肠道损伤。将大鼠分为七组：Ck（溶剂对照组）、HCk（高原对照组）、PAsp（平原阿司匹林处理组）、HAsp（高原阿司匹林处理组）、RSVL（低剂量白藜芦醇处理组）、RSVM（中剂量白藜芦醇处理组）和RSVH（高剂量白藜芦醇处理组）。实验期间每7天记录大鼠体重。实验最后一天，采集大鼠空肠组织进行苏木精-伊红染色（H&E），并采集大鼠粪便进行肠道菌群分析和代谢产物分析。结果表明，RSV可抑制高原缺氧环境下阿司匹林给药引起的体重减轻和肠道损伤。此外，它显著提高了白细胞介素（IL）-10和超氧化物歧化酶（SOD）的表达水平，同时大幅降低了肿瘤坏死因子-α、IL-1β和髓过氧化物酶（MPO）的表达水平。此外，16SrRNA基因序列分析表明，阿司匹林和RSV均改变了大鼠肠道微生物群的组成和结构。代谢组学结果表明，RSV改变了阿司匹林诱导的大鼠肠道损伤的肠道代谢产物，降低了2-羟基-3-（4-羟基苯基）丙酸和3-[(1-羧基乙烯基)氧基]苯甲酸的含量，增加了香豆酰、3-氨基-4-羟基苯甲酸和L-肉碱的含量。白藜芦醇可通过调节肠道菌群和代谢产物减轻高原缺氧环境下NSAID（阿司匹林）诱导的肠道损伤，其中RSVM组（50mg/kg）效果最佳。
