中国药科大学学报2026，Vol.57Issue(1)：90-97,8.DOI:10.11665/j.issn.1000-5048.2025050803
白术内酯Ⅰ调控cGAS/STING通路对扩张型心肌病小鼠心肌线粒体功能的影响
Effect of atractylenolide Ⅰ on myocardial mitochondrial function in mice with dilated cardiomyopathy by regulating cGAS/STING pathway
摘要
Abstract
This study aimed to investigate the effect of atractylenolide I(Atr-I)on myocardial mitochondrial function in mice with dilated cardiomyopathy(DCM)by regulating the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)pathway.Sixty SPF-grade male cTnT R141W transgenic DCM mice were randomly divided into the DCM group,Atr-I low-dose group(60 mg/kg),Atr-I high-dose group(240 mg/kg),captopril group(0.01 g/kg),and Atr-I high-dose+cGAS/STING pathway activator 5,6-dimethylxanthenone-4-acetic acid(DMXAA)group,with 12 mice in each group.Additionally,12 male C57BL/6J mice were used as the control group.All mice were administered via oral gavage once daily for 8 weeks.Cardiac function was assessed using the Vevo 770 ultrasound system;myocardial pathology was examined via HE staining;mitochondrial ultrastructure in cardiomyocytes was observed using transmission electron microscopy;the proportion of cardiomyocytes without reduced mitochondrial membrane potential was detected using JC-1 staining;reactive oxygen species(ROS)content in myocardial tissue was measured using 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining;adenosine triphosphate(ATP)content in myocardial tissue was determined using a commercial kit;and Western blot was performed to detect the protein expression levels of mitofusin-2(MFN2),dynamin-related protein 1(DRP1),cGAS,STING,interferon-β(IFN-β),CXC chemokine ligand 10(CXCL10),and interleukin-6(IL-6)in myocardial tissue.The aim was to observe the effect of Atr-I on myocardial mitochondrial function in DCM mice.The results showed that low-and high-dose Atr-I(60 mg/kg,240 mg/kg)intervention improved cardiac function,alleviated cardiomyocyte hypertrophy and disordered muscle fiber arrangement,ameliorated mitochondrial ultrastructure in cardiomyocytes,reduced ROS content and the protein expression levels of DRP1,cGAS,STING,IFN-β,CXCL10,and IL-6 in myocardial tissue,and increased the proportion of cardiomyocytes without reduced mitochondrial membrane potential,as well as ATP content and MFN2 protein expression in myocardial tissue.However,DMXAA attenuated the beneficial effects of high-dose Atr-I on myocardial mitochondrial function in DCM mice.In conclusion,Atr-I may improve myocardial mitochondrial function in DCM mice by inhibiting the cGAS/STING pathway.关键词
白术内酯Ⅰ/扩张型心肌病/线粒体功能/cGAS/STING通路Key words
atractylenolide Ⅰ/dilated cardiomyopathy/mitochondrial function/cGAS/STING pathway分类
医药卫生引用本文复制引用
王洪兴,张会超,李志伟,于晓芳..白术内酯Ⅰ调控cGAS/STING通路对扩张型心肌病小鼠心肌线粒体功能的影响[J].中国药科大学学报,2026,57(1):90-97,8.基金项目
河南省中医药科学研究专项课题(2024ZY2088) （2024ZY2088）
河南省中医药传承与创新人才工程(仲景工程)中医药青苗人才培养项目(豫卫中医函[2021]16号) （仲景工程）
河南省科技攻关项目(252102310485) This study was supported by the Special Scientific Research Project of Traditional Chinese Medicine in Henan Province(2024ZY2088),the Project for Cultivating Young Talents in Traditional Chinese Medicine of the Henan Province's Project for Inheriting and Innovating TCM Talents(Zhongjing Project)(Henan Health Commission TCM Letter No.16[2021]),and Henan Province's Science and Technology Research Project(252102310485) （252102310485）
