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聚焦肝脏巨噬细胞以阻止非酒精性脂肪性肝病的损伤和进展。

Spotlight on liver macrophages for halting injury and progression in nonalcoholic fatty liver disease.

机构信息

Department of Medicine, Randers Regional Hospital, Randers, Denmark.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Expert Opin Ther Targets. 2022 Aug;26(8):697-705. doi: 10.1080/14728222.2022.2132145. Epub 2022 Oct 14.

Abstract

INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and is rapidly emerging as the leading cause of liver-related morbidity and mortality. Macrophages play an essential role in the development and progression of NAFLD.

AREAS COVERED

In this review, we provide an update on recent studies of drugs, which directly or indirectly affect macrophages in NAFLD, and discuss the implication of macrophage biomarkers to monitor the disease stage and progression/regression.

EXPERT OPINION

There is an unmet need for a better understanding of disease pathogenesis from hepatic fat accumulation to disease progression with inflammation and fibrosis. We expect that future research will uncover additional objects/pathways as treatment targets. We speculate that this will involve better characterization of the gut microbiome, damage-associated molecular patterns (DAMPS) or molecules and pathways involved in the development of DAMPS, and advanced molecular biology studies including single-cell sequencing of macrophage subpopulations. In addition, we speculate that studies focusing on pharmaceuticals that improve insulin resistance, diminish the metabolic syndrome, and reduce fibrosis will prevail.

摘要

简介

非酒精性脂肪性肝病(NAFLD)被认为是代谢综合征在肝脏的表现,它正在迅速成为与肝脏相关的发病率和死亡率的主要原因。巨噬细胞在 NAFLD 的发生和发展中起着至关重要的作用。

涵盖领域

在这篇综述中,我们提供了关于直接或间接影响 NAFLD 中巨噬细胞的药物的最新研究,并讨论了巨噬细胞生物标志物在监测疾病阶段和进展/消退中的意义。

专家意见

从肝脂肪堆积到炎症和纤维化的疾病进展,人们对疾病发病机制的认识仍存在未满足的需求。我们预计未来的研究将揭示更多的治疗靶点。我们推测这将涉及对肠道微生物组、损伤相关分子模式(DAMPS)或 DAMPS 形成过程中涉及的分子和途径的更好描述,以及包括巨噬细胞亚群的单细胞测序在内的先进分子生物学研究。此外,我们推测,关注改善胰岛素抵抗、减少代谢综合征和减少纤维化的药物的研究将占主导地位。

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