Page 97 - 《中国药科大学学报》2026年第1期

第 57 卷第 1 期 王洪兴，等：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 91

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.
Key words atractylenolide I; dilated cardiomyopathy; mitochondrial function; cGAS/STING pathway

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)

扩张型心肌病（dilated cardiomyopathy，DCM） 供了新机制，也为治疗 DCM 提供了潜在的候选药
的特征是心室扩张和心肌收缩能力受损，通常会导 物与新颖靶点。
致心功能不全、心律失常，严重时还会导致心力衰
1 材 料
[1]
竭 。尽管近年来 DCM 的治疗方法有所改善，但
DCM 的预后仍然很差，凸显了寻找新疗法的重要 1.1 试 剂
性 。越来越多的证据表明线粒体功能异常在 Atr-I（纯度≥98%，成都瑞芬思德丹生物科技
[2]
[3]
DCM 进展中发挥着重要的作用 ，提示改善心肌线 有限公司）；卡托普利（规格 12.5mg，中美上海施
粒体功能可能有利于 DCM 的治疗。白术内酯Ⅰ 贵宝制药有限公司）；cGAS/STING 通路激活剂
（atractylenolide I，Atr-I）是白术的活性成分，具有抗 5,6-二甲基呫吨酮-4-乙酸（5,6-dimethylxanthenone-
[4]
炎和心肌保护等多种作用 。已有研究报道，Atr-I 4-acetic acid， DMXAA， 美 国 MedChemExpress 公
[5]
可改善心肌缺血再灌注大鼠心肌线粒体功能 。但 司）；单细胞悬液分离试剂盒（江苏凯基生物技术
Atr-I 是否可改善 DCM 小鼠心肌线粒体功能尚不 股份有限公司）；JC-1 染液（上海语纯生物科技有限
清楚。相关研究显示，环磷酸鸟苷-腺苷酸合成酶 公 司 ） ； 2 ′,7 ′ -二 氯 二 氢 荧 光 素 二 乙 酸 酯 （ 2',7'-
（cyclic GMP-AMP synthase，cGAS）/干扰素基因刺 dichlorodihydrofluorescein diacetate， DCFH-DA） 荧
激因子（stimulator of interferon genes，STING）通路 光探针（北京索莱宝科技有限公司）；心肌组织腺苷
的激活可导致糖尿病心肌病小鼠心功能异常 。但 三磷酸（adenosine triphosphate，ATP）检测试剂盒
[6]
Atr-I 是否可通过调控 cGAS/STING 通路改善 DCM （上海碧云天生物技术股份有限公司）；兔源一抗线
小鼠心肌线粒体功能尚不清楚。因此，本实验主要 粒体融合蛋白 2（mitofusin 2，MFN2）、动力相关蛋
探究 Atr-I 对 DCM 小鼠心肌线粒体功能的影响及 白 1（ dynamin-related protein 1， DRP1） 、 GAPDH、
初步机制，这不仅为理解 Atr-I 的心肌保护作用提 cGAS、STING、β-干扰素（interferon-β，IFN-β）、CXC