中国药物警戒 ›› 2026, Vol. 23 ›› Issue (6): 621-629.
DOI: 10.19803/j.1672-8629.20260430

• 心脑血管中药作用机制与安全性评价专栏（二） • 上一篇    下一篇

补土汤激活AKT/Bcl-2信号轴抑制心肌细胞凋亡改善大鼠心力衰竭机制研究

李艳君1, 刘呈祥2, 汤波1, 柳翼3, 张久亮3, 姜国臣4,*, 白雪5#   

  1. 1日照市中医医院心血管病科,山东 日照 276800;
    2日照市中医医院脑病科,山东 日照 276800;
    3中日友好医院中西医结合心内科,北京 100029;
    4清华大学第一附属医院中医科,北京 100016;
    5中国中医科学院医学实验中心,北京市中医药防治重大疾病基础研究重点实验室,北京 100700
  • 收稿日期:2026-05-27 出版日期:2026-06-15 发布日期:2026-06-18
  • 通讯作者: *姜国臣,男,硕士,副主任医师,中药防治心脑血管疾病。E-mail: 332527157@qq.com。#为共同通信作者。
  • 作者简介:李艳君,女,博士,主治医师,中药防治心血管病。
  • 基金资助:
    国家自然科学基金资助项目（82304767、82204670）; 山东省中医药科技项目（2021Q020）; 日照市博士后资金（417619）

Roles of Butu Decoction in Improving Heart Failure in Rats by Activating AKT/Bcl-2 Signaling Axis and Inhibiting Cardiomyocyte Apoptosis

LI Yanjun1, LIU Chengxiang2, TANG Bo1, LIU Yi3, ZHANG Jiuliang3, JIANG Guochen4,*, BAI Xue5#   

  1. 1Department of Cardiology, Rizhao Hospital of Traditional Chinese Medicine, Rizhao Shandong 276800, China;
    2Department of Neurology, Rizhao Hospital of Traditional Chinese Medicine, Rizhao Shandong 276800, China;
    3Cardiology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing 100029, China; 4Department of Traditional Chinese Medicine, the First Hospital of Tsinghua University, Beijing 100016, China;
    5Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Disease, Beijing 100700, China
  • Received:2026-05-27 Online:2026-06-15 Published:2026-06-18

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摘要： 目的 探讨补土汤改善心力衰竭（以下简称“心衰”）SD大鼠心功能的作用及其激活AKT/Bcl-2信号通路抑制心肌细胞凋亡的分子机制。方法 采用左前降支结扎术建立雄性SD大鼠心衰模型,将30只成模SD大鼠随机分为模型组（n=10）、补土汤组（n=10）、马来酸依那普利组（n=10）,另设假手术组（n=10）,连续灌胃给药4周。超声心动图检测大鼠心脏功能;苏木精-伊红（HE）与Masson染色观察心肌组织病理学形态及纤维化程度;ELISA检测血清脑钠肽（BNP）含量;网络药理学与分子对接技术挖掘补土汤治疗心衰的潜在核心靶点与活性成分;TUNEL法评估心肌梗死边缘区心肌细胞凋亡率;Western Blot法检测心肌梗死边缘区总蛋白激酶B1（AKT1）、磷酸化AKT1（pAKT1）及凋亡相关蛋白Bcl-2、Bax、Caspase-3表达水平。结果 动物实验显示,与模型组相比,补土汤组大鼠左室收缩末期内径（LVESD）及左室舒张末期内径（LVEDD）显著减小（P<0.01）,左室射血分数（LVEF）及左室短轴缩短率（LVFS）显著升高（P<0.01）;心肌病理形态显著改善,胶原纤维增生程度及血清BNP水平显著降低（P<0.01）。网络药理学及分子对接提示,补土汤中的木犀草素、槲皮素等主要活性成分与细胞凋亡及生长调控核心靶点AKT1具有较强的结合活性。机制研究表明,补土汤显著降低心肌梗死边缘区心肌细胞的凋亡率（P<0.01）;对总AKT1蛋白水平无明显影响,但显著上调pAKT1蛋白（P<0.05）及抗凋亡蛋白Bcl-2表达（P<0.01）,下调促凋亡蛋白Bax（P<0.05）及Caspase-3（P<0.01）表达,使Bcl-2/Bax比值显著升高（P<0.05）。结论 补土汤可有效改善心衰大鼠的心室重构并提升心脏功能,其机制可能与激活AKT信号通路,进而调控Bcl-2/Bax家族蛋白表达以抑制心肌细胞凋亡密切相关。

关键词: 补土汤, 心力衰竭, AKT信号通路, Bcl-2/Bax, 细胞凋亡, 心肌细胞, 大鼠

Abstract: Objective To explore the effect of Butu decoction on cardiac function of SD rats with heart failure (HF) and its molecular mechanism against cardiomyocyte apoptosis via the AKT/Bcl-2 signaling pathway. Methods Left anterior descending branch ligation was performed on male SD rats to establish an HF model. The surviving model rats were randomly divided into a model group (n=10), a Butu decoction group (n=10), and an enalapril maleate group (n=10). A sham surgery group was also established (n=10). Four weeks after intragastric administration, the cardiac function was detected via ultrasound. HE staining was used to observe myocardial histopathological changes, and Masson staining the degree of myocardial fibrosis. ELISA was employed to detect BNP contents in serum. Network pharmacology combined with molecular docking was used to identify the potential core targets and active components of Butu decoction against HF. TdT-mediated dUTP Nick-End Labeling (TUNEL) was adopted to determine the apoptosis rate of cells in regions bordering the infarction in rats. The protein expression levels of AKT1, pAKT1, Bax, Bcl-2 and Caspase-3 in these regions were detected via Western Blot. Results Results of animal experiments showed that the levels of LVESD and LVEDD in the Butu decoction group significantly decreased compared with the model group (P<0.01), while those of LVEF and LVFS significantly increased (P<0.01). HE staining suggested that the pathomorphology of rats in the Butu decoction group improved compared to the model group. The degree of myocardial fibrosis and the serum levels of BNP in the Butu decoction group were significantly reduced (P<0.01). Network pharmacology and molecular docking found that the main active components of Butu decoction, such as luteolin and quercetin, showed strong binding activity to AKT1, a core target regulating cell apoptosis and growth. Mechanistic studies suggested that Butu decoction significantly reduced the apoptosis rate of cardiomyocytes in regions bordering the infarction (P<0.01). This decoction had no obvious effect on the total protein level of AKT1, but markedly upregulated the expression of pAKT1 (P<0.05) and the anti-apoptotic protein Bcl-2 (P<0.01) while downregulating the pro-apoptotic proteins Bax (P<0.05) and Caspase-3 (P<0.01). Meanwhile, the Bcl-2/Bax ratio was significantly increased (P<0.05). Conclusion Butu decoction can improve ventricular remodeling and cardiac function in rats with heart failure, possibly by activating the AKT pathway, regulating Bcl-2/Bax proteins and inhibiting cardiomyocyte apoptosis.

Key words: Butu Decoction, Heart Failure, AKT Signaling Pathway, Bcl-2/Bax, Apoptosis, Cardiomyocyte, Rats

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