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青蒿琥酯通过 lncRNA MALAT1/PTBP1/IFIH1 轴调控巨噬细胞极化缓解脓毒症诱导的肝损伤。

Artesunate alleviates sepsis-induced liver injury by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.

机构信息

Department of Medical Intensive Care Unit, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou City, Fujian Province, China.

Department of Medical Intensive Care Unit, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou City, Fujian Province, China.

出版信息

Diagn Microbiol Infect Dis. 2024 Sep;110(1):116383. doi: 10.1016/j.diagmicrobio.2024.116383. Epub 2024 Jun 6.

DOI:10.1016/j.diagmicrobio.2024.116383
PMID:38889486
Abstract

BACKGROUND

The present study aimed to explore the regulatory effects of artesunate on macrophage polarization in sepsis.

METHODS

Cell models and mice models were established using lipopolysaccharide (LPS), followed by treatment with various concentrations of artesunate. The phenotype of the macrophages was determined by flow cytometry. RNA immunoprecipitation was used to confirm the binding between MALAT1 and polypyrimidine tract-binding protein 1 (PTBP1), as well as between PTBP1 and interferon-induced helicase C domain-containing protein 1 (IFIH1).

RESULTS

Treatment with artesunate inhibited M1 macrophage polarization in Kupffer cells subjected to LPS stimulation by downregulating MALAT1. Furthermore, MALAT1 abolished the inhibitory effect of artesunate on M1 macrophage polarization by recruiting PTBP1 to promote IFIH. In vivo experiments confirmed that artesunate alleviated septic liver injury by affecting macrophage polarization via MALAT1.

CONCLUSION

The present study showed that artesunate alleviates LPS-induced sepsis in Kupffer cells by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis.

摘要

背景

本研究旨在探讨青蒿琥酯对脓毒症中巨噬细胞极化的调节作用。

方法

采用脂多糖(LPS)建立细胞模型和小鼠模型,并用不同浓度的青蒿琥酯进行处理。通过流式细胞术确定巨噬细胞的表型。RNA 免疫沉淀用于确认 MALAT1 与多嘧啶 tract 结合蛋白 1(PTBP1)以及 PTBP1 与干扰素诱导的螺旋酶 C 结构域蛋白 1(IFIH1)之间的结合。

结果

青蒿琥酯通过下调 MALAT1 抑制 LPS 刺激的库普弗细胞中 M1 巨噬细胞的极化。此外,MALAT1 通过招募 PTBP1 促进 IFIG1 来消除青蒿琥酯对 M1 巨噬细胞极化的抑制作用。体内实验证实,青蒿琥酯通过 MALAT1 影响巨噬细胞极化来减轻脓毒症引起的肝损伤。

结论

本研究表明,青蒿琥酯通过 lncRNA MALAT1/PTBP1/IFIH1 轴调节巨噬细胞极化来缓解 LPS 诱导的库普弗细胞脓毒症。

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