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人参根茎通过抑制雄性 C57BL/6J 小鼠自噬增强美托洛尔在慢性心力衰竭中的作用。

Ginseng Radix et Rhizoma enhanced the effect of metoprolol in chronic heart failure by inhibiting autophagy in male C57BL/6J mice.

机构信息

Key Laboratory of Pharmacology of Traditional Chinese Medical Formulea, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

出版信息

PLoS One. 2024 Aug 14;19(8):e0301875. doi: 10.1371/journal.pone.0301875. eCollection 2024.

Abstract

BACKGROUND

Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol is widely used in patients with HF. However, there is no report on the combined effects of GS and metoprolol in patients with HF.

OBJECTIVE

This study investigated the combined effects of GS and metoprolol in male C57BL/6J mice with HF and the underlying mechanisms.

MATERIALS AND METHODS

We utilized a mouse myocardial HF model to measure the serum levels of creatine kinase (CK) and creatine kinase-MB form (CK-MB) using an automated biochemical analyzer. Lactate dehydrogenase (LDH) and cardiac troponin (cTnT) levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed by Western blotting.

RESULTS

GS combined with metoprolol improved heart function, reduced heart damage, and decreased serum levels of CK, CK-MB, LDH, and cTnT. The combination of GS and metoprolol decreased autophagy in myocardial cells by reducing the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5) and increasing the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR.

CONCLUSION

GS enhanced the anti-heart failure effect of metoprolol. Its mechanism of action might be related to the inhibition of autophagy mediated by the activation of the PI3K/Akt/mTOR pathway.

摘要

背景

人参(GS)常被用作心力衰竭(HF)患者的辅助治疗药物。美托洛尔广泛用于 HF 患者。然而,尚无关于 GS 与美托洛尔联合用于 HF 患者的报道。

目的

本研究旨在探讨 GS 与美托洛尔联合应用于 HF 雄性 C57BL/6J 小鼠的效果及其潜在机制。

材料和方法

采用小鼠心肌 HF 模型,应用自动生化分析仪测定血清肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)的水平,酶联免疫吸附试验测定乳酸脱氢酶(LDH)和心肌肌钙蛋白 T(cTnT)的水平。利用透射电镜评估心肌细胞自噬,并用 Western blot 分析与自噬相关的信号通路蛋白的变化。

结果

GS 与美托洛尔联合应用可改善心功能,减轻心脏损伤,降低血清 CK、CK-MB、LDH 和 cTnT 水平。GS 与美托洛尔联合应用可通过降低自噬相关蛋白(LC3、p62、Beclin1 和 Atg5)的水平,增加 p-PI3K/PI3K、p-Akt/Akt 和 p-mTOR/mTOR 的比值,减少心肌细胞自噬。

结论

GS 增强了美托洛尔的抗心力衰竭作用。其作用机制可能与激活 PI3K/Akt/mTOR 通路抑制自噬有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11324128/d82175e497c1/pone.0301875.g001.jpg

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