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基于代谢组学探讨肾安胶囊对草酸钙结晶诱导早期肾损伤的预防作用机制

The mechanism of the preventive effect of Shen'an capsule on the calcium oxalate crystal-induced early renal injury based on metabolomics.

作者信息

Fan Wei, Hou Jiebin, Zhu Weiye, Zhang Shuyue, Shao Keda, Quan Feiyu, Chen Wei

机构信息

No. 425 Hospital of PLA, Sanya, China.

Changhai Hospital, Second Military Medical University, Shanghai, China.

出版信息

Biomed Chromatogr. 2018 Dec;32(12):e4374. doi: 10.1002/bmc.4374. Epub 2018 Oct 17.

DOI:10.1002/bmc.4374
PMID:30141275
Abstract

Kidney stone disease is a worldwide metabolism-associated disorder with a high incidence of renal dysfunction. However, effective methods to prevent crystalline nephropathy are still lacking owing to the absence of aetiological research. Shen'an (SA) capsules are prepared from Chinese medicinal compounds and are considered a promising treatment for the prevention of crystal-induced renal injury. In this study, 24 mice were randomly divided into four groups: saline, oxalate, SA-treated (via preventive administration) and SA-only groups. A metabolomics analysis based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to explore the plasma metabolic profiles among the different groups. The amount of crystal deposition and the decline in kidney function were significantly alleviated by the use of SA capsule. A total of 24 metabolites that showed a reversal trend following SA capsule administration were identified as plasma biomarkerss of the preventive effects of SA capsules on crystal-induced renal injury. Most of these metabolites were involved in the metabolisms of lipid metabolism, energy metabolism, glutathione metabolism and vitamin metabolism. In conclusion, SA capsules exert a preventive effect in mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways.

摘要

肾结石病是一种全球范围内与代谢相关的疾病,肾功能障碍发病率很高。然而,由于病因学研究的缺乏,仍然缺乏预防结晶性肾病的有效方法。肾安(SA)胶囊由中药复方制成,被认为是预防晶体诱导肾损伤的一种有前景的治疗方法。在本研究中,24只小鼠被随机分为四组:生理盐水组、草酸盐组、SA治疗组(通过预防性给药)和仅SA组。基于超高效液相色谱-四极杆飞行时间质谱联用(UPLC-Q-TOF/MS)进行代谢组学分析,以探索不同组之间的血浆代谢谱。使用SA胶囊可显著减轻晶体沉积量和肾功能下降。共有24种在SA胶囊给药后呈现逆转趋势的代谢物被鉴定为SA胶囊对晶体诱导肾损伤预防作用的血浆生物标志物。这些代谢物大多参与脂质代谢、能量代谢、谷胱甘肽代谢和维生素代谢。总之,SA胶囊通过调节多种代谢途径对晶体诱导肾损伤的小鼠发挥预防作用。

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