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源自外泌体的小RNA对非酒精性脂肪性肝病的保护作用。

Protective effects of small RNAs encapsulated in -derived exosomes against non-alcoholic fatty liver disease.

作者信息

Xu Min, Ma Longjun, Liang Hongwei, Tang Wei, Gu Shouyong

机构信息

Geriatric Hospital of Nanjing Medical University, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, China.

Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Front Pharmacol. 2025 Jan 6;15:1476820. doi: 10.3389/fphar.2024.1476820. eCollection 2024.

Abstract

INTRODUCTION

, a traditional medicinal plant, is renowned for its therapeutic properties, including the promotion of anti-inflammatory and bile secretion. Notably, it has demonstrated efficacy in the treatment of jaundice. This study aimed to evaluate the potential of -derived exosomes (ACDEs) as a novel therapeutic approach in non-alcoholic fatty liver disease (NAFLD).

METHODS

The physicochemical properties of ACDEs were isolated and characterized using differential centrifugation, and the therapeutic efficacy was evaluated in an methionine-choline-deficient (MCD) diet induced NAFLD mouse model. , mouse hepatocytes were treated with palmitic acid (PA) to simulate a high fat environment. Intracellular triglycerides (TG) and total cholesterol (TC) levels were quantified, and Oil Red O staining was assessed. Additionally, the expression levels of proteins and RNAs associated with lipogenesis and inflammation were analyzed.

RESULTS

The NAFLD mouse model exhibited notable liver damage, including lipid deposition and inflammatory responses. However, treatment with ACDEs exhibited broad pharmacological activities, effectively reversing hepatic lipid accumulation and inflammatory damage. experiments revealed that ACDEs were internalized by AML12 cells via macropinocytosis and caveolin-mediated endocytosis. This treatment ameliorated dysregulated lipid metabolism and inhibited inflammatory responses. High throughput sequencing further identified a distinct small RNA profile in ACDEs, indicating the potential involvement in interspecies physiological regulation.

DISCUSSION

In conclusion, this study provides evidence for the therapeutic potential of ACDEs in NAFLD and offers a novel perspective for the development of Artemisia capillaris-based therapies for NAFLD, related metabolic disorders, and hepatitis.

摘要

引言

茵陈蒿,一种传统药用植物,以其治疗特性而闻名,包括促进抗炎和胆汁分泌。值得注意的是,它已证明在治疗黄疸方面有效。本研究旨在评估茵陈蒿衍生的外泌体(ACDEs)作为非酒精性脂肪性肝病(NAFLD)新治疗方法的潜力。

方法

使用差速离心法分离并表征ACDEs的物理化学性质,并在蛋氨酸 - 胆碱缺乏(MCD)饮食诱导的NAFLD小鼠模型中评估其治疗效果。此外,用棕榈酸(PA)处理小鼠肝细胞以模拟高脂肪环境。定量细胞内甘油三酯(TG)和总胆固醇(TC)水平,并评估油红O染色。另外,分析与脂肪生成和炎症相关的蛋白质和RNA的表达水平。

结果

NAFLD小鼠模型表现出明显的肝损伤,包括脂质沉积和炎症反应。然而,ACDEs治疗表现出广泛的药理活性,有效逆转肝脏脂质积累和炎症损伤。实验表明,ACDEs通过巨胞饮作用和小窝蛋白介导的内吞作用被AML12细胞内化。这种治疗改善了失调的脂质代谢并抑制了炎症反应。高通量测序进一步确定了ACDEs中独特的小RNA谱,表明其可能参与种间生理调节。

讨论

总之,本研究为ACDEs在NAFLD中的治疗潜力提供了证据,并为开发基于茵陈蒿的NAFLD、相关代谢紊乱和肝炎治疗方法提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e599/11743690/b6ae7854a698/fphar-15-1476820-g001.jpg

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