目的 本实验旨在探讨慢性萎缩性胃炎(CAG)的发病机制,筛选其潜在的生物标志物。方法 采用脱氧胆酸钠溶液和氨水溶液配合饥饱失常法建立慢性萎缩性胃炎的模型,造模10周后,收集模型组与对照组大鼠的血浆及胃组织,检测血浆生化指标及胃组织的病理状况。造模期间收集0、4、6、8、10周模型大鼠的尿液,采用1H-NMR的技术监测CAG大鼠不同造模时期尿液的代谢轮廓,并利用多元统计分析方法和相对距离公式刻画其代谢轮廓的动态变化。结果 通过代谢轮廓变化图发现造模第8周的损伤程度最大,并比较对照组与模型第8周的大鼠尿液代谢差异,筛选出了18种与CAG密切相关的潜在生物标志物,并发现它们分别参与了缬氨酸、亮氨酸和异亮氨酸的生物合成、TCA循环、肠道菌群代谢、甘氨酸、丝氨酸和苏氨酸代谢、脂肪酸代谢、嘌呤代谢和尿素循环7条代谢途径,经MetPA分析显示,甘氨酸、丝氨酸和苏氨酸代谢、三羧酸循环(TCA)和缬氨酸、亮氨酸和异亮氨酸的生物合成3条代谢途径为CAG发展最重要的代谢途径。结论 慢性萎缩性胃炎的发病机制可能与甘氨酸、丝氨酸和苏氨酸代谢、TCA循环和缬氨酸、亮氨酸和异亮氨酸的生物合成3条代谢途径的变化有关,为CAG的发病机制研究奠定基础。
Abstract
OBJECTIVE To explore the mechanism of chronic atrophic gastritis (CAG) and screen the potential biomarkers. METHODS CAG model was established in rats by using sodium deoxycholate solution and aqueous ammonia solution in combination with hunger and satiety method. After 10 weeks, the plasma and gastric tissues of model rats and control rats were collected to detect plasma biochemical parameters and pathological conditions of gastric tissues. The urine of model rats at 0, 4, 6, 8, and 10 weeks was collected during modeling, and 1H-NMR technique was used to monitor the metabolic profile of urine in different modeling periods of CAG rats. Multivariate statistical analysis method and relative distance formula were used to describe the dynamic changes of its metabolic profile. RESULTS Significant differences in urine metabolism were found between the control group and the model group at the 8th week. Eighteen potential biomarkers of CAG were screened out, which participated in the biosynthesis of valine, leucine and isoleucine, TCA cycle, gut flora metabolism, glycine, serine and threonine metabolism, fatty acid metabolism, purine metabolism, and urea cycle. MetPA analysis demonstrated that glycine, serine and threonine metabolism, TCA cycle, valine, leucine and isoleucine biosynthesis are the most important metabolic pathway for CAG development. CONCLUSION The pathogenesis of chronic atrophic gastritis may be related to the changes of glycine, serine and threonine metabolism, TCA cycle and the biosynthesis of valine, leucine and isoleucine. This finding laid the foundation for the study of the pathogenesis of CAG.
关键词
慢性萎缩性胃炎 /
动态代谢组学 /
潜在生物标志物 /
机制研究
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Key words
chronic atrophic gastritis /
dynamic metabolomics /
potential biomarker /
mechanism research
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中图分类号：
R965
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参考文献
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脚注
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基金
国家自然科学基金项目资助(31570346;81703697)
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