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从连续性肾脏替代治疗角度揭示血浆氧化脂质在慢加急性肾损伤进展中的免疫调节作用

Unveiling the immunomodulator role of plasma oxidized lipids in SA-AKI progression: a CRRT perspective.

作者信息

Zhou Lu, Li Huirong, Guo Wenfeng, Feng Lan, Hu Jiangtao, Liu Jing, Wang Tingting, Liu Hongbao

机构信息

Department of Nephrology, Tangdu Hospital, The Fourth Military Medical University, Air Force Medical University, Xi'an, Shaanxi Province, China.

出版信息

Front Physiol. 2024 Dec 23;15:1412235. doi: 10.3389/fphys.2024.1412235. eCollection 2024.

Abstract

BACKGROUND

Plasma oxidized lipids are intimately linked to immune regulation as bioactive mediators. However, it is not clear whether they are related to the progression of sepsis-associated acute kidney injury (SA-AKI) and the effect of continuous renal replacement therapy (CRRT). This study intends to explore the changes in certain oxidized lipid during CRRT treatment and their correlation with the immune microenvironment and prognosis by analyzing plasma oxidative lipidomics.

METHODS

A total of 48 SA-AKI patients undergoing CRRT for more than 72 h were enrolled in this prospective cohort study. Oxidative lipidomics was analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometric (UPLC-MS/MS) detection at the beginning of CRRT (T0) and 72 h later (T72), respectively.

RESULTS

Compared with survivors, plasma EETs, EpOMEs and EpDPEs in non-survivors were significantly down-regulated at T0, while PGFs, TXB and HEPEs were up-regulated. After 72 h of CRRT, DiHETEs were significantly up-regulated and PGFs were down-regulated in non-survivors, while HEPEs and EpOMEs were up-regulated and 6keto-PGF1α was down-regulated in survivors. KEGG annotation showed that the differential lipids of survivors before and after CRRT were mainly enriched and up-regulated in metabolic pathway.

CONCLUSION

This study provided a comprehensive overview of plasma oxidized lipids in SA-AKI patients undergoing CRRT and further elucidated the lipids and pathways linked to patient severity and prognosis. Additionally, we unveiled the potential mechanisms by which CRRT improves the prognosis of SA-AKI patients by removing PGFs and TXs while simultaneously upregulating HEPE to ameliorate the immune microenvironment, as well as the potential significance of adjusting CRRT prescriptions based on plasma oxidized lipidomics.

摘要

背景

血浆氧化脂质作为生物活性介质与免疫调节密切相关。然而,尚不清楚它们是否与脓毒症相关性急性肾损伤(SA-AKI)的进展以及连续性肾脏替代治疗(CRRT)的效果有关。本研究旨在通过分析血浆氧化脂质组学来探讨CRRT治疗期间某些氧化脂质的变化及其与免疫微环境和预后的相关性。

方法

本前瞻性队列研究共纳入48例接受CRRT超过72小时的SA-AKI患者。分别在CRRT开始时(T0)和72小时后(T72)通过超高效液相色谱-串联质谱(UPLC-MS/MS)检测分析氧化脂质组学。

结果

与幸存者相比,非幸存者血浆中的环氧二十碳三烯酸(EETs)、环氧十八碳三烯酸(EpOMEs)和环氧二十二碳五烯酸(EpDPEs)在T时间点显著下调,而前列腺素F(PGFs)、血栓素B(TXB)和羟二十碳四烯酸(HEPEs)上调。CRRT治疗72小时后,非幸存者中双羟二十碳四烯酸(DiHETEs)显著上调,PGFs下调,而幸存者中HEPEs和EpOMEs上调,6-酮-前列腺素F1α(6keto-PGF1α)下调。京都基因与基因组百科全书(KEGG)注释显示,幸存者CRRT前后的差异脂质主要在代谢途径中富集并上调。

结论

本研究全面概述了接受CRRT的SA-AKI患者血浆中的氧化脂质,并进一步阐明了与患者严重程度和预后相关的脂质及途径。此外,我们揭示了CRRT通过清除PGFs和TXs同时上调HEPEs来改善免疫微环境从而改善SA-AKI患者预后的潜在机制,以及基于血浆氧化脂质组学调整CRRT处方的潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa14/11701052/f72ce96d8cf8/fphys-15-1412235-g001.jpg

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