高原肠胃安方对高原缺氧所致肠损伤的保护作用及机制

doi:10.19803/j.1672-8629.20260108

摘要/Abstract

摘要： 目的考察高原肠胃安方对高原低压低氧导致小鼠肠道损伤的保护作用。方法 C57BL/6J小鼠分为对照组,低氧模型组,阳性药物组（复方谷氨酰胺0.8 g·kg^-1·d^-1）,高原肠胃安方低（7.3 g·kg^-1·d^-1）、中（14.6 g·kg^-1·d^-1）、高（29.2 g·kg^-1·d^-1）剂量组,每组8只。连续灌胃给药14 d,对照组与模型组给予等量蒸馏水灌胃,采用低压低氧致小鼠胃肠应激损伤模型。造模条件为低压低氧氧舱模拟海拔7 000 m处理3 d,通过酶联免疫吸附法检测小鼠血清中肠道损伤标志物D-乳酸、二胺氧化酶含量变化;以酶联免疫吸附法检测肠组织的炎症因子（IL-1β、TNF-α、IL-6）、氧化应激指标变化[4-羟基壬烯醛（4-HNE）、丙二醛（MDA）、超氧化物歧化酶（SOD）、还原性谷胱甘肽（GSH）]。苏木精-伊红（HE）染色与电镜观察小鼠肠组织损伤,蛋白免疫印迹法检测肠紧密连接蛋白表达（ZO-1、Occludin）,收集小鼠新鲜粪便以16S rRNA测序检测肠道菌群。结果高原肠胃安方干预可以减轻肠损伤小鼠体重下降的程度（P<0.05）,降低损伤标志物D-LA、DAO（P<0.000 1）,抑制炎症因子IL-1β、TNF-α、IL-6水平（P<0.05）,抑制氧化应激指标4-HNE、MDA、SOD、GSH水平（P<0.05）,上调肠道连接蛋白ZO-1、Occludin（P<0.01）。调控脑肠轴激素抑制5-HT与SP分泌（P<0.05）,减轻肠道上皮细胞损伤,并且调控肠道菌群平衡,增加肠道菌群中益生菌例如乳杆菌属Lactobacillus、阿克曼菌属Akkermansia的相对含量。结论高原肠胃安方对小鼠因高原缺氧所致的肠道损伤具有保护作用,可能的作用机制与调节肠道菌群平衡、抑制炎症反应、拮抗氧化应激有关。

关键词: 高原肠胃安方, 高原, 低压低氧, 肠道损伤, 炎症, 氧化应激, 肠道菌群, 小鼠

Abstract: Objective To investigate the protective effect of Gaoyuan Changweian formula (GYW) against intestinal injury induced by hypobaric hypoxia in mice. Methods C57BL/6J mice were divided into the following groups (n=8 each): a normal control (NC) group, a hypobaric hypoxia model (MOD) group, a positive control (compound glutamine, 0.8 g·kg^-1·d^-1) group, and GYW-treated groups at low (7.3 g·kg^-1·d^-1), medium (14.6 g·kg^-1·d^-1), and high (29.2 g·kg^-1·d^-1) doses. Each of these groups received oral administration for 14 consecutive days except the NC and MOD groups that were given an equal volume of distilled water. A model for hypobaric hypoxia-induced intestinal stress injury was established by exposing mice to conditions simulating 7 000 m altitude in a hypobaric oxygen chamber for 3 days. Serum levels of intestinal injury markers, D-lactate (D-LA) and diamine oxidase (DAO), were measured by enzyme-linked immunosorbent assay (ELISA). The levels of inflammatory cytokines (IL-1β, TNF-α, IL-6) and oxidative stress markers (4-HNE, MDA, SOD, GSH) in intestinal tissues were also detected by ELISA. Intestinal tissue damage was observed via hematoxylin and eosin (HE) staining and electron microscopy. The expression of intestinal tight junction proteins (ZO-1, occludin) was analyzed by Western blotting. Fresh fecal samples were collected, and gut microbiota composition was assessed by 16S rRNA gene sequencing. Results GYW intervention alleviated the decrease in body weight of mice with intestinal injury (P<0.05), significantly lowered the levels of injury markers D-LA and DAO (P<0.000 1), inhibited the inflammatory response (P<0.05) and oxidative stress (P<0.05), and upregulated the expressions of the tight junction proteins ZO-1 and occludin (P<0.01). Furthermore, GYW treatment regulated the brain-gut axis by suppressing the secretion of 5-HT and SP (P<0.05), mitigated damage to intestinal epithelial cells, modulated gut microbiota balance, and increased the relative abundance of probiotics. Conclusion Gaoyuan Changweian formula exerts a protective effect against intestinal injury caused by high-altitude hypoxia in mice. The underlying mechanism may be associated with the regulation of gut microbiota balance, inhibition of the inflammatory response, and antagonism of oxidative stress.

Key words: Gaoyuan Changweian Formula, High-Altitude, Hypobaric and Hypoxia, Intestinal Injury, Inflammation, Oxidative Stress, Gut Microbiota, Mice

中图分类号:

江儒蛟, 李芳, 王宇光, 李茂星, 汤响林, 张娴勰, 高月, 马增春. 高原肠胃安方对高原缺氧所致肠损伤的保护作用及机制[J]. 中国药物警戒, 2026, 23(4): 383-389.

JIANG Rujiao, LI Fang, WANG Yuguang, LI Maoxing, TANG Xianglin, ZHANG Xianxie, GAO Yue, MA Zengchun. Protective Effects of Gaoyuan Changweian Formula against Intestinal Injury Induced by High-Altitude Hypoxia[J]. Chinese Journal of Pharmacovigilance, 2026, 23(4): 383-389.

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https://zgywjj.magtechjournal.com/CN/Y2026/V23/I4/383

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