School of Pharmacy, Shenyang Pharmaceutical University, Benxi 117004, China.
School of Pharmacy, Shenyang Pharmaceutical University, Benxi 117004, China.
J Pharm Biomed Anal. 2021 Jan 30;193:113705. doi: 10.1016/j.jpba.2020.113705. Epub 2020 Oct 19.
Based on the traditional Chinese medicine theory, kidney is considered to govern the bones and dominate the store of essence ('jing' in Chinese). Gushudan (GSD) is a traditional Chinese medicine prescription for the treatment osteoporosis in the clinic and is beneficial for improving kidney function and strengthening bone in vivo. This study aims to reveal the renal metabolic profiling of glucocorticoid-induced osteoporosis (GIOP) rats and the potential preventive effect of GSD based on an integrative metabolomic and metallomic approach. Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS) were combined for the investigation of renal metabolomic and metallomic profiling. In the metabolomic analysis, 17 potential biomarkers were found to be related to GIOP, such as glucose, malate, γ-aminobutyric acid and arachidonic acid. And seven metallic elements, including Zn, Mn, Se, Fe, Mo, As and Ba, were identified in rat kidney tissue in the metallomic analysis. The major metabolic pathways included aerobic glycolysis, and neurotransmitter amino acids metabolism. It was worth mentioning that the levels of trace metal elements (Zn, Mn, Se, Fe, As and Ba) significantly reduced in the model group, while the contents of Zn, Mn, Se, Fe and As were elevated after administration of GSD. Finally, a correlation metabolic regulatory network and the metabolic pathways associated with trace metal elements were further investigated to illuminate the role of potential biomarkers and trace metal elements in GIOP rats. These variations of potential biomarkers and trace metal elements suggested the existence of kidney damage and metabolic disorder in GIOP rats, which indicated a close relationship between bone and kidney in vivo. Moreover, the integrated renal metabolomic and metallomic profiling could be as an effective supplementary measure to the plasma and urine metabolomic research, and it was helpful to further understand the holistic formation process of osetoporosis and the potential preventive effects of GSD on GIOP rats.
基于中医理论，肾被认为主骨，藏精。骨疏丹（GSD）是一种治疗骨质疏松症的中药方剂，有利于改善肾功能，增强体内骨骼。本研究旨在采用整合代谢组学和金属组学方法，揭示糖皮质激素诱导的骨质疏松症（GIOP）大鼠的肾脏代谢特征，以及 GSD 的潜在预防作用。气相色谱-质谱联用（GC-MS）和电感耦合等离子体质谱（ICP-MS）联合用于研究肾脏代谢组学和金属组学特征。在代谢组学分析中，发现了 17 个与 GIOP 相关的潜在生物标志物，如葡萄糖、苹果酸、γ-氨基丁酸和花生四烯酸。在金属组学分析中，鉴定出 7 种金属元素，包括锌、锰、硒、铁、钼、砷和钡，存在于大鼠肾脏组织中。主要代谢途径包括有氧糖酵解和神经递质氨基酸代谢。值得一提的是，模型组中痕量金属元素（锌、锰、硒、铁、砷和钡）水平显著降低，而 GSD 给药后锌、锰、硒、铁和砷的含量升高。最后，进一步研究了相关代谢调节网络和与痕量金属元素相关的代谢途径，以阐明潜在生物标志物和痕量金属元素在 GIOP 大鼠中的作用。这些潜在生物标志物和痕量金属元素的变化表明，GIOP 大鼠存在肾脏损伤和代谢紊乱，提示体内骨骼与肾脏之间存在密切关系。此外，整合的肾脏代谢组学和金属组学分析可以作为血浆和尿液代谢组学研究的有效补充手段，有助于进一步了解骨质疏松症的整体形成过程和 GSD 对 GIOP 大鼠的潜在预防作用。
