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阿司匹林抑制脂氧合酶途径:对 HIV 预防的意义。

Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention.

机构信息

Laboratory of Viral Immunology, Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.

Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.

出版信息

Prostaglandins Other Lipid Mediat. 2024 Oct;174:106878. doi: 10.1016/j.prostaglandins.2024.106878. Epub 2024 Jul 29.

DOI:10.1016/j.prostaglandins.2024.106878
PMID:39084323
Abstract

BACKGROUND

1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown.

METHODS

Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy.

RESULTS

Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA.

CONCLUSIONS

Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

摘要

背景

2021 年有 150 万人新感染了 HIV,这表明需要新的预防方法。炎症通过将 HIV 靶细胞吸引到女性生殖道(FGT)来增加感染 HIV 的风险。在一项试点研究中,乙酰水杨酸(ASA/阿司匹林)将 FGT HIV 靶细胞的比例降低了 35%。然而,其机制尚不清楚。

方法

肯尼亚内罗毕的女性每天服用低剂量的 ASA(81mg),持续 6 周。通过高效液相色谱-串联质谱法对血浆中的游离氧化脂进行定量分析。

结果

检测到 9 种脂肪酸底物的氧化脂,其中 4 种底物的超过一种分析物在 ASA 后减少。综合分析发现,ASA 下调了环氧化酶和脂氧化酶,但不影响细胞色素 P450 活性,n-6/n-3 氧化脂谱降低,表明 ASA 后炎症减轻。

结论

炎症与脂氧化酶活性增加和 HIV 风险增加有关。我们的数据表明,ASA 通过下调氧化脂来减轻炎症。了解 ASA 如何减轻炎症可能会导致新的 HIV 预防方法。

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