| 黄芪甲苷衍生物治疗慢性心力衰竭小鼠的药效评价及作用机制研究 |
| 投稿时间：2023-10-03 修订日期：2024-02-18 点此下载全文 |
| 引用本文：景凯,杨慈荣,张圳,臧艺蓓,刘霞.黄芪甲苷衍生物治疗慢性心力衰竭小鼠的药效评价及作用机制研究[J].药学实践杂志,2024,42(5):190~197 |
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| 基金项目:国家自然科学基金（82273920） |
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| 中文摘要:目的 对黄芪甲苷系列衍生物治疗慢性心力衰竭的药效学进行评价，筛选候选化合物，初步探讨候选化合物黄芪甲苷衍生物HHQ16抗心衰的作用机制。方法 采用左冠状动脉前降支结扎四周诱导C57BL/6小鼠慢性心衰模型，将小鼠分为假手术组、模型组、阳性对照卡托普利组、系列黄芪甲苷衍生物组，共4组。小鼠灌胃给药4周，超声心动检测心功能，筛选出治疗心衰的最优黄芪甲苷衍生物HHQ16。进一步对HHQ16进行初步机制研究，通过大体形态学观察心脏的大小变化；HE染色观察心脏的病理变化；Masson染色观察心肌胶原沉积；免疫组化染色检测心肌纤维化指标Ⅰ型胶原（COL1）、III型胶原（COL3）、α平滑肌肌动蛋白（αSMA）蛋白水平变化；qPCR技术测定心肌纤维化指标COL1、COL3、αSMA和转化生长因子β1（TGF-β1）mRNA水平的变化。结果 黄芪甲苷衍生物均能显著增加左室射血分数（LVEF）和左室短轴缩短率（LVFS），改善心功能，以HHQ16为最优化合物。与模型组相比，HHQ16组心脏体积显著减小，心肌肥大减轻，心肌组织胶原沉积显著下降，心肌纤维化指标COL1、COL3、αSMA和TGF-β1 mRNA水平以及COL1、COL3、αSMA蛋白水平显著降低。结论 HHQ16是治疗小鼠心衰的最优黄芪甲苷衍生物，它通过改善心肌重塑，抑制心肌肥大和心肌纤维化，改善心功能。 |
| 中文关键词:黄芪甲苷衍生物 慢性心力衰竭 心功能 心肌纤维化 |
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| Efficacy and mechanism of astragaloside Ⅳ derivatives on chronic heart failure in mice |
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| Abstract:Objective To evaluate the pharmacodynamics of astragaloside Ⅳ derivatives for chronic heart failure, screen the candidate compounds and preliminarily explore the mechanism of the candidate compound HHQ16 against heart failure. Methods Chronic heart failure was induced by left anterior descending artery ligation in C57BL/6 mice for 4 weeks, and the mice were divided into 4 groups, including sham group, model group, positive control captopril group, and astragaloside Ⅳ derivatives group. After continuous intragastric administration for four weeks, the cardiac function was detected by echocardiography, and the optimal astragaloside Ⅳ derivative HHQ16 was selected for the treatment of heart failure. The preliminary mechanism for HHQ16 was further explored. The size of heart was observed by gross morphology; pathological changes were observed by HE staining; collagen deposition in the myocardium was observed by Masson staining; protein levels of myocardial fibrosis indexes COL1, COL3, and αSMA were detected by immunohistochemical staining, and mRNA levels of myocardial fibrosis indexes COL1, COL3, αSMA, and TGF-β1 were determined by qPCR technique. Results All astragaloside Ⅳ derivatives significantly improved cardiac function with increasing LVEF and LVFS, of which HHQ16 was the optimal compound. Compared with the model group, the heart volume of HHQ16 group was significantly reduced; myocardial hypertrophy was reduced; collagen deposition in myocardial tissues was reduced; and myocardial fibrosis indexes, COL1, COL3, αSMA and TGF-β1 mRNA levels, as well as the protein levels of COL1, COL3 and αSMA were significantly reduced. Conclusion HHQ16 is an optimal astragaloside Ⅳ derivatives for the treatment of chronic heart failure in mice, which could improve cardiac function by improving myocardial remodeling, and inhibit myocardial hypertrophy and myocardial fibrosis. |
| keywords:astragaloside Ⅳ derivative chronic heart failure cardiac function myocardial fibrosis |
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