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通过调节PPAR-，抑制miR-128-3p减轻阿霉素引发的小鼠急性心脏损伤。

Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-.

作者信息

Zhang Wen-Bin, Zheng Yong-Fa, Wu Yao-Gui

机构信息

Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

出版信息

PPAR Res. 2021 Apr 20;2021:7595374. doi: 10.1155/2021/7595374. eCollection 2021.

DOI:10.1155/2021/7595374
PMID:33986789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8079209/
Abstract

BACKGROUND

The clinical usefulness of doxorubicin (DOX), an anthracycline with antitumor activity, is limited by its cardiotoxicity. Oxidative stress and myocardial apoptosis were closely associated with DOX-induced cardiac dysfunction. It has been reported that microRNA-128-3p (miR-128-3p) was involved into the regulation of redox balance. However, the role of miR-128-3p in DOX-related cardiac injury remains not yet understood. The aim of this study was to investigate the biological effect of miR-128-3p in DOX-induced cardiotoxicity.

METHODS

To induce DOX-related acute cardiac injury, mice were subjected to a single injection of DOX. Inhibition of myocardial miR-128-3p was achieved by an adeno-associated virus (AAV9) system carrying a miR-128-3p sponge.

RESULTS

The data in our study indicated that miR-128-3p was upregulated in DOX-treated hearts and cardiomyocytes. Inhibition of miR-128-3p attenuated DOX-related cardiac injury and improved cardiac function in mice. Moreover, miR-128-3p inhibition could suppress myocardial inflammatory response, oxidative damage, and cell apoptotic death in DOX-treated mice. Further analysis showed that miR-128-3p could directly target peroxisome proliferator-activated receptor (PPAR-) and decrease PPAR- expression. Moreover, the protective effects provided by miR-128-3p inhibition were abolished by a PPAR- antagonist in vivo and in vitro.

CONCLUSIONS

miR-128-3p inhibition attenuated DOX-related acute cardiac injury via the regulation of PPAR- in mice.

摘要

背景

阿霉素（DOX）是一种具有抗肿瘤活性的蒽环类药物，其临床应用因心脏毒性而受到限制。氧化应激和心肌细胞凋亡与DOX诱导的心脏功能障碍密切相关。据报道，微小RNA-128-3p（miR-128-3p）参与氧化还原平衡的调节。然而，miR-128-3p在DOX相关心脏损伤中的作用尚不清楚。本研究旨在探讨miR-128-3p在DOX诱导的心脏毒性中的生物学作用。

方法

为诱导DOX相关的急性心脏损伤，给小鼠单次注射DOX。通过携带miR-128-3p海绵的腺相关病毒（AAV9）系统抑制心肌miR-128-3p。

结果

我们的研究数据表明，miR-128-3p在DOX处理的心脏和心肌细胞中上调。抑制miR-128-3p可减轻DOX相关的心脏损伤，并改善小鼠心脏功能。此外，抑制miR-128-3p可抑制DOX处理小鼠的心肌炎症反应、氧化损伤和细胞凋亡死亡。进一步分析表明，miR-128-3p可直接靶向过氧化物酶体增殖物激活受体（PPAR-）并降低PPAR-表达。此外，PPAR-拮抗剂在体内和体外均消除了抑制miR-128-3p所提供的保护作用。

结论

在小鼠中，抑制miR-128-3p通过调节PPAR-减轻DOX相关的急性心脏损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/79b4f4db7b62/PPAR2021-7595374.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/c2f7846bc0a3/PPAR2021-7595374.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/f9dc579e1636/PPAR2021-7595374.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/2ec713c12cbd/PPAR2021-7595374.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/8894271975ba/PPAR2021-7595374.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/ddca54c48fbb/PPAR2021-7595374.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/768fe01bd39f/PPAR2021-7595374.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/79b4f4db7b62/PPAR2021-7595374.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/c2f7846bc0a3/PPAR2021-7595374.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/f9dc579e1636/PPAR2021-7595374.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/2ec713c12cbd/PPAR2021-7595374.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/8894271975ba/PPAR2021-7595374.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/ddca54c48fbb/PPAR2021-7595374.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/768fe01bd39f/PPAR2021-7595374.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe3/8079209/79b4f4db7b62/PPAR2021-7595374.007.jpg

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