黄连解毒汤对自发性高血压大鼠心肌线粒体自噬作用的研究

doi:10.5246/jcps.2025.09.062

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (9): 850-859.DOI: 10.5246/jcps.2025.09.062

黄连解毒汤对自发性高血压大鼠心肌线粒体自噬作用的研究

李永梅¹^,^#, 王源¹^,^#, 张晓明², 高艺文¹, 辛春红¹^,^*(), 张楠¹^,^*()

^1. 滨州医学院烟台附属医院, 山东烟台 264100
^2. 滨州医学院, 山东烟台 264100

收稿日期:2025-03-13 修回日期:2025-04-11 接受日期:2025-04-23 出版日期:2025-10-02 发布日期:2025-10-02
通讯作者: 辛春红, 张楠

Impact of Huanglian Jiedu decoction on myocardial mitochondrial autophagy in spontaneously hypertensive rats

Yongmei Li¹^,^#, Yuan Wang¹^,^#, Xiaoming Zhang², Yiwen Gao¹, Chunhong Xin¹^,^*(), Nan Zhang¹^,^*()

¹ Yantai Affiliated Hospital of Binzhou Medical College, Yantai 264100, Shandong, China
² Binzhou Medical University, Yantai 264100, Shandong, China

Received:2025-03-13 Revised:2025-04-11 Accepted:2025-04-23 Online:2025-10-02 Published:2025-10-02
Contact: Chunhong Xin, Nan Zhang
About author:
^# Yongmei Li and Yuan Wang contributed equally to this work.
Supported by:
The Shandong Provincial Key Project of TCM Science and Technology (Grant Nos. M-2023170, M-2022233), and the Binzhou Medical College Student Innovation and Entrepreneurship Training Program (Grant Nos. X202410440414, X2024225030120).

摘要/Abstract

摘要：

高血压是最常见的心血管疾病之一, 自噬在心血管疾病的发生发展中起到重要作用, 本研究观察黄连解毒汤(Huanglian Jiedu decoction, HLJDD)对自发性高血压大鼠(Spontaneous Hypertension Rats, SHRs)心肌线粒体自噬的影响, 进一步探讨自噬与心肌重塑、损伤的相互关系。将SHRs随机分为模型组、HLJDD低剂量组、HLJDD中剂量组、HLJDD高剂量组以及阳性对照组(卡托普利)5个组别, 另设Wistar-Kyoto (WKY)大鼠为空白对照组, 每组各10只。模型组和空白对照组分别经口灌胃给予相同体积的生理盐水, 其余各给药组分别经口灌胃给予相对应的药物。灌胃结束后, 检测各组大鼠血压(包括收缩压、舒张压和平均动脉压), 线粒体肿胀度和膜电位的改变, 游离ATPase活性的变化, 自噬相关因子mRNA和蛋白的变化。结果发现, HLJDD可以降低SHRs的血压(包括收缩压, 舒张压和平均动脉压), 升高线粒体肿胀度和膜电位, 增加线粒体ATPase活性, 降低自噬相关基因(AKT、mTOR、Beclin-1、LC3-II)的mRNA和蛋白的表达水平。本研究显示HLJDD有效改善SHRs心肌组织损伤, 其机制可能是与减少心肌细胞线粒体的自噬, 从而发挥对心脏的保护作用有关。

关键词: 黄连解毒汤, 自发性高血压, 线粒体, 自噬, 心肌损伤

Abstract:

Hypertension is one of the most prevalent cardiovascular diseases, and autophagy is known to play a significant role in the pathogenesis and progression of cardiovascular conditions. This study aimed to evaluate the effects of Huanglian Jiedu decoction (HLJDD) on myocardial mitochondrial autophagy in spontaneously hypertensive rats (SHRs) and to further explore the relationship between autophagy, myocardial remodeling, and injury. The SHRs were randomly assigned to five groups: the model group, the HLJDD low-dose group, the HLJDD medium-dose group, the HLJDD high-dose group, and a positive control group treated with captopril. Additionally, a blank control group was established using Wistar Kyoto (WKY) rats, with 10 rats in each group. The model and blank control groups were administered an equivalent volume of physiological saline via oral gavage, while the treatment groups received their respective doses of HLJDD or captopril by oral gavage. Following the treatments, various parameters were assessed, including blood pressure (systolic, diastolic, and mean arterial pressure), mitochondrial swelling and membrane potential, free ATPase activity, as well as the mRNA and protein levels of autophagy-related factors. The results showed that HLJDD significantly reduced blood pressure (systolic, diastolic, and mean arterial pressure) in SHR rats. Moreover, it enhanced mitochondrial swelling and membrane potential, increased mitochondrial ATPase activity, and decreased the mRNA and protein expression levels of autophagy-related genes (AKT, mTOR, Beclin-1, and LC3-II) in SHRs. The findings of this study suggested that HLJDD could effectively ameliorate myocardial tissue injury in SHRs, and its protective effects on the heart might be attributed to the reduction of autophagy in cardiomyocyte mitochondria. This provided insights into the potential therapeutic use of HLJDD in managing hypertension-induced myocardial injury and remodeling.

Key words: Huanglian Jiedu decoction, Spontaneous hypertension, Mitochondria, Autophagy, Myocardial injury

Supporting:

李永梅, 王源, 张晓明, 高艺文, 辛春红, 张楠. 黄连解毒汤对自发性高血压大鼠心肌线粒体自噬作用的研究[J]. 中国药学(英文版), 2025, 34(9): 850-859.

Yongmei Li, Yuan Wang, Xiaoming Zhang, Yiwen Gao, Chunhong Xin, Nan Zhang. Impact of Huanglian Jiedu decoction on myocardial mitochondrial autophagy in spontaneously hypertensive rats[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(9): 850-859.

图/表 6

Table 1. qPCR primer information.

Figure 1. Effects of HLJDD on systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHRs (n = 10, x ± s). Note: *P < 0.05, compared with the normal group; #P < 0.05, compared with the model group; ΔP < 0.05, compared with the positive control group.

Figure 2. Effects of HLJDD on myocardial mitochondrial swelling and membrane potential in rats (n = 10, x ± s). Note: *P < 0.05, compared with the normal group; #P < 0.05, compared with the model group; ΔP < 0.05, compared with the positive control group.

Figure 3. Comparison of mitochondrial free ATPase activity in each group (x ± s, μmol/L). Note: *P < 0.05, compared with the normal group; #P < 0.05, compared with the model group; ΔP < 0.05, compared with the positive control group.

Figure 4. Effects of HLJDD on AKT, mTOR, Beclin-1, LC3-II mRNA in SHRs (n = 10, x ± s). Note: *P < 0.05, compared with the normal group; #P < 0.05, compared with the model group; ΔP < 0.05, compared with the positive control group.

Figure 5. Effects of HLJDD on the expression of AKT, mTOR, Beclin-1and LC3-II proteins in the myocardium of SHRs (n = 10, x ± s). (A) Expression of mTOR, AKT, Beclin-1 and LC3-II proteins. Note: *P < 0.05, compared with the normal group; #P < 0.05, compared with the model group; ΔP < 0.05, compared with the positive control group; (B) AKT and mTOR Western blot images; (C) Beclin-1 and LC3-II Western blot images (A. Blank; B. Low-dose group; C. Middle-dose group; D. High-dose group; E. Positive; F. Model).

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黄连解毒汤对自发性高血压大鼠心肌线粒体自噬作用的研究

Impact of Huanglian Jiedu decoction on myocardial mitochondrial autophagy in spontaneously hypertensive rats

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