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中性粒细胞膜工程化人参根衍生外泌体负载的miRNA 182-5p靶向NOX4/Drp-1/NLRP3信号通路减轻脓毒症急性肺损伤：实验研究

Neutrophil membrane-engineered Panax ginseng root-derived exosomes loaded miRNA 182-5p targets NOX4/Drp-1/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies.

作者信息

Ma Chunhua, Liu Kun, Wang Fei, Fei Xiaochun, Niu Chaochao, Li Tao, Liu Liangming

机构信息

State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Research Department of Army Medical Center, Army Medical University, Chongqing.

Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.

出版信息

Int J Surg. 2024 Jan 1;110(1):72-86. doi: 10.1097/JS9.0000000000000789.

DOI:10.1097/JS9.0000000000000789
PMID:37737899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10793765/
Abstract

BACKGROUND

The purpose of this study was to prepare neutrophil membrane-engineered Panax ginseng root-derived exosomes (N-exo) and investigate the effects of N-exo microRNA (miRNA) 182-5p (N-exo-miRNA 182-5p) on acute lung injury (ALI) in sepsis.

METHODS

Panax ginseng root-derived exosomes were separated by differential centrifugation. Neutrophil membrane engineering was performed on exo to obtain N-exo. miRNA182-5p was transmitted into N-exo by electroporation technology to obtain N-exo-miRNA 182-5p. LPS was used to establish an in-vivo and in-vitro model of ALI of sepsis to evaluate the anti-inflammatory effect of N-exo-miRNA 182-5p.

RESULTS

The results of transmission electron microscope showed that exo was a double-layer membrane structure like a saucer. Nanoparticle size analysis showed that the average particle size of exo was 129.7 nm. Further, compared with exo, the level of miRNA182-5p was significantly increased in N-exo. The experimental results showed that N-exo-miRNA 182-5p significantly improved ALI via target regulation of NOX4/Drp-1/NLRP3 signal pathway in vivo and in vitro .

CONCLUSION

In conclusion, this study prepared a novel engineered exosome (N-exo and N-exo-miRNA 182-5p significantly improved ALI in sepsis via target regulation of NOX4/Drp-1/NLRP3 signal pathway, providing new ideas and methods for treatment of ALI in sepsis.

摘要

背景

本研究旨在制备中性粒细胞膜工程化人参根衍生外泌体（N-外泌体），并研究N-外泌体微小RNA（miRNA）182-5p（N-外泌体-miRNA 182-5p）对脓毒症急性肺损伤（ALI）的影响。

方法

采用差速离心法分离人参根衍生外泌体。对外泌体进行中性粒细胞膜工程处理以获得N-外泌体。通过电穿孔技术将miRNA182-5p导入N-外泌体以获得N-外泌体-miRNA 182-5p。使用脂多糖建立脓毒症ALI的体内和体外模型，以评估N-外泌体-miRNA 182-5p的抗炎作用。

结果

透射电子显微镜结果显示，外泌体为碟状双层膜结构。纳米颗粒大小分析显示，外泌体的平均粒径为129.7nm。此外，与外泌体相比，N-外泌体中miRNA182-5p的水平显著升高。实验结果表明，N-外泌体-miRNA 182-5p在体内和体外通过靶向调控NOX4/Drp-1/NLRP3信号通路显著改善ALI。

结论

总之，本研究制备了一种新型工程化外泌体（N-外泌体和N-外泌体-miRNA 182-5p），其通过靶向调控NOX4/Drp-1/NLRP3信号通路显著改善脓毒症中的ALI，为脓毒症ALI的治疗提供了新的思路和方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4a/10793765/85f372bc3ad1/js9-110-072-g010.jpg
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