二氢丹参酮 I 通过促进心肌缺血再灌注损伤后的淋巴管生成改善心脏功能

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY European journal of pharmacology Pub Date : 2025-02-15 Epub Date: 2025-01-01 DOI:10.1016/j.ejphar.2024.177245
Ya-Chao Wang, Yan Zhu, Wan-Ting Meng, Yan Zheng, Xiao-Qi Guan, Chang-le Shao, Xiu-Ya Li, Dan Hu, Ming-Zhu Wang, Hai-Dong Guo
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引用次数: 0

摘要

二氢丹参酮I (DHT)是从丹参中提取的一种有效成分。既往研究表明DHT可改善心肌缺血再灌注损伤(IR)大鼠心功能。然而,DHT改善大鼠心肌损伤的机制仍需进一步研究。新生淋巴管可减轻大鼠心肌梗死后的心肌水肿、炎症和纤维化,改善心功能。本研究分别采用超声心动图、马氏三色染色、免疫组织化学和Western blot检测大鼠心功能变化、梗死区胶原纤维沉积及淋巴管生成相关指标水平。用siVE-cadherin和siVEGFR-3转染人淋巴内皮细胞(HLECs),通过CCK8、TUNEL、transwell、伤口愈合和成管实验检测DHT对HLECs细胞活力、迁移和成管的影响。我们发现DHT处理心肌IR大鼠,与淋巴管生成相关的LYVE-1、PROX1、VEGF-C、VEGFR-3、IGF-1、podoplanin和IGF-1R水平升高,维持内皮细胞功能的VE-cadherin水平升高。DHT可降低I/R后的炎症因子水平和心肌细胞凋亡,从而改善心功能。为了探讨DHT促进淋巴管生成的机制,我们构建H2O2和OGD/R损伤HLECs模型,模拟体外心肌IR微环境。结果表明,DHT可减轻HLECs的损伤和凋亡。另一方面,DHT可增强HLECs中VEGFR-3和VE-cadherin的表达,促进细胞迁移和小管形成。敲除VEGFR-3或VE-cadherin后,DHT对HLECs小管形成和迁移的影响明显减弱。我们的研究提出DHT可以通过增强淋巴管生成来改善IR后的心功能,有助于心肌IR治疗方法的发展。
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Dihydrotanshinone I improves cardiac function by promoting lymphangiogenesis after myocardial ischemia-reperfusion injury.

Dihydrotanshinone I (DHT) is an active ingredient derived from Salvia miltiorrhiza. Previous studies have demonstrated that DHT can improve cardiac function in rats with myocardial ischemia-reperfusion injury (IR). However, the mechanism by which DHT improves myocardial injury in rats still requires further research. Lymphangiogenesis can reduce myocardial edema, inflammation, and fibrosis after myocardial infarction in rats, and improve cardiac function. In this study, the changes in cardiac functions, collagen fiber deposition in the infarcted area and the level of relevant indicators of lymphangiogenesis were examined by echocardiography, Masson's trichrome staining, immunohistochemistry and Western blot, respectively. Human lymphatic endothelial cells (HLECs) were transfected with siVE-cadherin and siVEGFR-3, and the effects of DHT on HLEC cell viability, migration and tube formation were detected through CCK8, TUNEL, transwell, wound healing and tube formation assay. We found that in myocardial IR rats treated with DHT, the levels of LYVE-1, PROX1, VEGF-C, VEGFR-3, IGF-1, podoplanin and IGF-1R, which are associated with lymphangiogenesis, were increased, as well as the level of VE-cadherin, which maintains endothelial cell function. DHT reduced the levels of inflammatory factors and myocardial cell apoptosis, thereby improving cardiac function after I/R. To explore the mechanism of DHT promoting lymphangiogenesis, H2O2 and OGD/R injury models of HLECs were constructed to simulate the microenvironment of myocardial IR in vitro. The results proved that DHT could reduce the damage and apoptosis of HLECs. On the other hand, DHT enhanced the expression of VEGFR-3 and VE-cadherin in HLECs, promoted cell migration and tube formation. The effects of DHT on the tube formation and migration of HLECs were significantly decreased after knocking down VEGFR-3 or VE-cadherin. Our research proposed that DHT could improve the heart function after IR through the enhancement of lymphangiogenesis and contributed to the development of the treatment methods for myocardial IR.

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来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
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