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辐射诱导的肝损伤和肝细胞衰老。

Radiation-induced liver injury and hepatocyte senescence.

作者信息

Zhu Wei, Zhang Xiaofen, Yu Mengli, Lin Bingru, Yu Chaohui

机构信息

Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Cell Death Discov. 2021 Sep 16;7(1):244. doi: 10.1038/s41420-021-00634-6.

Abstract

Radiation-induced liver injury (RILI) is a major complication of radiotherapy during treatment for liver cancer and other upper abdominal malignant tumors that has poor pharmacological therapeutic options. A series of pathological changes can be induced by radiation. However, the underlying mechanism of RILI remains unclear. Radiation can induce cell damage via direct energy deposition or reactive free radical generation. Cellular senescence can be observed due to the DNA damage response (DDR) caused by radiation. The senescence-associated secretory phenotype (SASP) secreted from senescent cells can cause chronic inflammation and aggravate liver dysfunction for a long time. Oxidative stress further activates the signaling pathway of the inflammatory response and affects cellular metabolism. miRNAs clearly have differential expression after radiation treatment and take part in RILI development. This review aims to systematically profile the overall mechanism of RILI and the effects of radiation on hepatocyte senescence, laying foundations for the development of new therapies.

摘要

放射性肝损伤(RILI)是肝癌和其他上腹部恶性肿瘤放疗过程中的主要并发症,其药物治疗选择有限。辐射可引发一系列病理变化。然而,RILI的潜在机制仍不清楚。辐射可通过直接能量沉积或活性自由基生成诱导细胞损伤。由于辐射引起的DNA损伤反应(DDR),可观察到细胞衰老。衰老细胞分泌的衰老相关分泌表型(SASP)可导致慢性炎症并长期加重肝功能障碍。氧化应激进一步激活炎症反应信号通路并影响细胞代谢。放疗后miRNAs明显存在差异表达,并参与RILI的发展。本综述旨在系统阐述RILI的整体机制以及辐射对肝细胞衰老的影响,为新疗法的开发奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b6/8446062/d8eb86588ef5/41420_2021_634_Fig1_HTML.jpg

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