灵龟柱肝汤通过 Wnt/β-catenin 信号通路延缓心肌梗死后慢性心力衰竭大鼠的心室重构。
Linggui Zhugan decoction delays ventricular remodeling in rats with chronic heart failure after myocardial infarction through the Wnt/β-catenin signaling pathway.
机构信息
Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China.
Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
出版信息
Phytomedicine. 2023 Nov;120:155026. doi: 10.1016/j.phymed.2023.155026. Epub 2023 Aug 16.
CONTEXT
Traditional Chinese medicine plays an important role in the prevention and treatment of heart failure (HF). Linggui Zhugan decoction has been approved for clinical treatment of chronic HF. However, the mechanism is still unclear.
OBJECTIVE
The effect of Linggui Zhugan decoction on the Wnt/β-catenin signaling pathway in rat myocardium was studied to investigate the mechanism by Linggui Zhugan decoction effects ventricular remodeling in rats with heart failure after myocardial infarction.
METHOD
A rat model of HF after myocardial infarction was prepared by ligating the left anterior descending coronary artery. After 6 weeks of intervention with Linggui Zhugan decoction, the effect of Linggui Zhugan decoction on the cardiac function of chronic HF model rats was observed. Myocardial infarct size was measured by triphenyl tetrazolium chloride (TTC) staining. Enzyme linked immunosorbent assays (ELISAs) were used to measure NT-proBNP and sST-2 concentrations in rat serum. Hematoxylin and eosin (H&E) staining, and Masson's trichrome staining were used to observe the morphology of myocardial tissue; immunohistochemistry was used to detect the protein expression of type I collagen and type III collagen in myocardial tissue; and mRNA expression levels of Wnt3a, GSK-3β, β-catenin, and c-Myc in the infarct marginal zone were detected using PCR. Protein expression of Wnt3a, p-GSK-3β, GSK-3β, and β-catenin in the infarct marginal zone was detected using western blot.
RESULTS
Compared with the control, Linggui Zhugan decoction reduced the levels of serum ST-2 and NT-proBNP, improved cardiac function, and reduced the deposition of collagen fiber. In addition, Linggui Zhugan decoction inhibited the expression of Wnt3a, p-GSK-3β, and β-catenin in cardiomyocytes.
CONCLUSION
Linggui Zhugan decoction inhibits the expression of several key proteins in the Wnt/β-catenin signaling pathway, delays cardiomyocyte hypertrophy and fibrosis, and improves cardiac function.
背景
中医药在心力衰竭（HF）的防治中发挥着重要作用。灵龟逐淤汤已被批准用于慢性 HF 的临床治疗。然而，其作用机制尚不清楚。
目的
研究灵龟逐淤汤对大鼠心肌中 Wnt/β-catenin 信号通路的影响，探讨灵龟逐淤汤对心肌梗死后心力衰竭大鼠心室重构的作用机制。
方法
结扎大鼠左前降支冠状动脉制备心肌梗死后 HF 大鼠模型，经灵龟逐淤汤干预 6 周后，观察灵龟逐淤汤对慢性 HF 模型大鼠心功能的影响。采用氯化三苯基四氮唑（TTC）染色法测量心肌梗死面积。酶联免疫吸附试验（ELISA）法检测大鼠血清中 NT-proBNP 和 sST-2 的浓度。苏木精-伊红（H&E）染色和 Masson 三色染色观察心肌组织形态；免疫组织化学法检测心肌组织中 I 型胶原和 III 型胶原的蛋白表达；采用 PCR 检测梗死边缘区 Wnt3a、GSK-3β、β-catenin 和 c-Myc 的 mRNA 表达水平；采用 Western blot 检测梗死边缘区 Wnt3a、p-GSK-3β、GSK-3β和β-catenin 的蛋白表达。
结果
与对照组相比，灵龟逐淤汤降低了血清 ST-2 和 NT-proBNP 水平，改善了心功能，减少了胶原纤维沉积。此外，灵龟逐淤汤抑制了心肌细胞中 Wnt3a、p-GSK-3β和 β-catenin 的表达。
结论
灵龟逐淤汤抑制了 Wnt/β-catenin 信号通路中几个关键蛋白的表达，延缓了心肌细胞肥大和纤维化，改善了心功能。
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