Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, P.R. China.
Department of Pharmacology, Shanxi Institute for Food and Drug Control, Taiyuan, P.R. China.
Rejuvenation Res. 2021 Apr;24(2):86-96. doi: 10.1089/rej.2020.2352. Epub 2020 Sep 29.
d-galactose (d-gal) is widely used to induce aging. However, it is still unclear whether long-term injection of d-gal affects the gastrointestinal functions of aging rats, and how. In this study, we investigated the effects of d-gal on the gastrointestinal functions of aging rats, especially from the perspective of fecal metabolomics. Biochemical and behavioral analyses were performed. Besides, a H NMR-based metabolomics approach was built and applied in combination with multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Regarding gastrointestinal functions, d-gal significantly decreased the small intestine propulsion rates and prolonged gastrointestinal transit time. In addition, d-gal significantly increased the oxidative damages. PCA results showed that d-gal interrupted the metabolic profiles of endogenous small molecules in aging rats. Furthermore, OPLS-DA showed that 40 metabolites were screened and identified to be involved in the disruption of gastrointestinal functions in aging rats. Accordingly, seven metabolic pathways were recognized as the most influenced pathways associated with gastrointestinal functions of aging rats induced by d-gal, including amino acid metabolism, energy metabolism, intestinal flora metabolism, and metabolism of short chain fatty acids. It is the first report to investigate the effects and underlying mechanisms of d-gal on gastrointestinal functions of aging rats from the perspective of fecal metabolomics. The current results are conducive to further comprehensively understand d-gal-induced aging and will expand the applications of d-gal in pharmacological researches.
d-半乳糖（d-gal）被广泛用于诱导衰老。然而，长期注射 d-gal 是否会影响衰老大鼠的胃肠道功能，以及影响的方式如何，目前尚不清楚。在这项研究中，我们从粪便代谢组学的角度研究了 d-gal 对衰老大鼠胃肠道功能的影响。进行了生化和行为分析。此外，建立了基于 1 H NMR 的代谢组学方法，并结合主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）等多变量数据分析进行了应用。关于胃肠道功能，d-gal 显著降低了小肠推进率并延长了胃肠道转运时间。此外，d-gal 显著增加了氧化损伤。PCA 结果表明，d-gal 中断了衰老大鼠内源性小分子的代谢谱。此外，OPLS-DA 显示筛选和鉴定出 40 种代谢物与衰老大鼠胃肠道功能紊乱有关。相应地，确定了 7 条与 d-gal 诱导衰老大鼠胃肠道功能相关的受影响程度最大的代谢途径，包括氨基酸代谢、能量代谢、肠道菌群代谢和短链脂肪酸代谢。这是首次从粪便代谢组学角度研究 d-gal 对衰老大鼠胃肠道功能的影响及其潜在机制的报道。目前的结果有助于进一步全面了解 d-gal 诱导的衰老，并将扩大 d-gal 在药理学研究中的应用。
