当期文章

骨骼肌特异性敲低ACSL1基因改善顺铂诱导的骨骼肌萎缩

王欢^1,2, 王浩哲^1,2, 谢江平¹, 王浩^1,2, 方文君^1,2, 李梦欠^1,2, 陈沛珊^1,2, 何文壁^1,2, 朱琳^1,2,3, 刘晓光^1,2,3,*

¹广州体育学院运动与健康学院，广州 510500；²广州体育学院体卫融合创新发展研究中心，广州 510500；³粤港澳大湾区体育科学创新研究中心，广州体育学院，广州510500

摘要

本研究旨在探究长链酰基辅酶A合成酶1 (long-chain acyl-CoA synthetase 1, ACSL1)在顺铂诱导骨骼肌萎缩模型中的作用以及机制。将野生型小鼠分为腹腔注射顺铂组和对照组。荧光定量PCR和有参转录组测序结果显示，顺铂组小鼠骨骼肌中ACSL1 基因相较于对照组显著上调，提示ACSL1 可能在顺铂诱导骨骼肌萎缩中发挥关键作用。为探究其作用及可能机制，本研究构建了靶向骨骼肌的ACSL1 低表达腺相关病毒，并通过腹腔注射顺铂构建了小鼠骨骼肌萎缩模型。免疫荧光染色结果显示，与仅接受顺铂干预小鼠相比，接受顺铂干预的ACSL1 基因敲低小鼠骨骼肌的肌纤维横截面积、最大直径、最小直径和平均直径均显著增加。RT-qPCR 结果和免疫组织化学染色结果显示，敲低骨骼肌ACSL1 基因可下调顺铂诱导骨骼肌萎缩中萎缩相关基因1 (atrophy-related gene 1, Atrogin-1)和自噬相关因子自噬相关16 样蛋白1 (autophagy related protein 16like protein 1, Atg16L1)、Atg12 和Atg7 mRNA 表达水平，上调肌细胞生成素(myogenin)蛋白表达水平，下调Toll 样受体4(Toll-like receptor 4, TLR4)蛋白表达水平，但是对顺铂诱导骨骼肌萎缩中铁死亡相关因子(除环氧合酶-2 外)和炎症相关因子[干扰素基因刺激因子(stimulator of interferon genes, STING)、TLR4 和TLR9] mRNA表达水平无明显影响。上述结果表明，骨骼肌特异性敲低ACSL1 基因可能通过下调Atrogin-1、TLR4 和自噬相关因子表达缓解顺铂诱导的骨骼肌萎缩。

关键词： ACSL1; 骨骼肌萎缩; 顺铂; 自噬; Atrogin-1

Skeletal muscle-specific knockdown of ACSL1 gene ameliorates cisplatin-induced skeletal muscle atrophy

WANG Huan^1,2, WANG Hao-Zhe^1,2, XIE Jiang-Ping¹, WANG Hao^1,2, FANG Wen-Jun^1,2, LI Men-Qian^1,2, CHEN Pei-Shan^1,2, HE Wen-Bi^1,2, ZHU Lin^1,2,3, LIU Xiao-Guang^1,2,3,*

¹School of Sport and Health, Guangzhou Sport University, Guangzhou 510500, China；²Research Center for Innovative Development of Sports and Healthcare Integration, Guangzhou Sport University, Guangzhou 510500, China；³Innovative Research Center for Sports Science in the Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou Sport University, Guangzhou 510500, China

Abstract

The aim of this study was to explore the role of long-chain acyl-CoA synthetase 1 (ACSL1) in cisplatin-induced skeletal muscle atrophy and the underlying mechanism. Wild-type mice were divided into cisplatin group and control group. The results of fluorescence quantitative PCR and sequencing of reference transcriptome showed that ACSL1 gene was significantly up-regulated in the skeletal muscle of cisplatin group compared with the control group, suggesting that ACSL1 may play a key role in cisplatin-induced skeletal muscle atrophy. To further investigate ACSL1's function and potential mechanism, the present study constructed an adeno-associated virus to achieve muscle-specific ACSL1 knockdown and established a cisplatin-induced skeletal muscle atrophy model. The results of immunofluorescence staining showed that compared with mice only receiving cisplatin intervention, mice receiving ACSL1 gene knockdown and cisplatin intervention had significantly increased muscle fiber cross-sectional area, maximum diameter, minimum diameter, and average diameter in their skeletal muscles. The results of RT-qPCR and immunohistochemical staining showed that knockdown of the ACSL1 gene in skeletal muscle down-regulated the mRNA expression levels of atrophy related gene 1 (Atrogin-1) and autophagy-related factors such as autophagy related protein 16 like protein 1 (Atg16L1), Atg12, and Atg7 in cisplatin-induced skeletal muscle atrophy, up-regulated the protein expression level of myogenin, and down-regulated Toll-like receptor 4 (TLR4) protein expression level, but had no significant effect on the mRNA expression levels of ferroptosis-related factors (except for cyclooxygenase-2) and inflammation-related factors such as stimulator of interferon genes (STING), Toll-like receptor 4 (TLR4) and TLR9 in cisplatin-induced skeletal muscle atrophy. These results suggest that specific knockdown of ACSL1 gene in skeletal muscle may alleviate cisplatin-induced skeletal muscle atrophy by down-regulating the expression of Atrogin-1, TLR4 and autophagy-related factors.

Key words: ACSL1; skeletal muscle atrophy; cisplatin; autophagy; Atrogin-1

收稿日期：　　录用日期：

通讯作者：刘晓光　　E-mail:

DOI: 10.13294/j.aps.2025.0093

引用本文：

王欢, 王浩哲, 谢江平, 方文君, 李梦欠, 陈沛珊, 何文壁, 朱琳, 刘晓光. 骨骼肌特异性敲低ACSL1基因改善顺铂诱导的骨骼肌萎缩[J]. 生理学报 2026; 78 (3): 616-630.

WANG Huan, WANG Hao-Zhe, XIE Jiang-Ping, FANG Wen-Jun, LI Men-Qian, CHEN Pei-Shan, HE Wen-Bi, ZHU Lin, LIU Xiao-Guang. Skeletal muscle-specific knockdown of ACSL1 gene ameliorates cisplatin-induced skeletal muscle atrophy. Acta Physiol Sin 2026; 78 (3): 616-630 (in Chinese with English abstract).