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Archive > Volume 17 Issue 1 > 2025,17(1):139-147. DOI:https://doi.org/10.1016/j.chmed.2023.12.007 Prev Next

芪參顆粒調(diào)控BMP2-Dll4-Notch1通路促進(jìn)血管新生保護(hù)心肌缺血的機(jī)制研究

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Qishen Granule protects against myocardial ischemia by promoting angiogenesis through BMP2-Dll4-Notch1 pathway

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    摘要:
    目的：治療性血管新生是治療缺血性心臟病（IHD）的一種有前景的方法。本研究旨在探討芪參顆粒（QSG）對(duì)心肌缺血中血管新生的影響及其潛在機(jī)制。 方法：采用大鼠心肌梗死模型進(jìn)行體內(nèi)實(shí)驗(yàn)研究。每日給予QSG 2.352 g/kg，持續(xù)四周。通過超聲心動(dòng)圖評(píng)估心功能，通過激光多普勒和CD31的免疫組化染色評(píng)估促血管新生。體外實(shí)驗(yàn)中構(gòu)建氧-葡萄糖剝奪（Oxygen-glucose deprivation, OGD）誘導(dǎo)的人臍靜脈內(nèi)皮細(xì)胞損傷模型。通過CCK8檢測細(xì)胞活力、劃痕實(shí)驗(yàn)檢測細(xì)胞遷移能力，體外成管實(shí)驗(yàn)檢測細(xì)胞成管能力。采用酶聯(lián)免疫吸附試驗(yàn)（ELISA）和蛋白質(zhì)印跡法（Western blots）評(píng)估BMP2-Dll4-Notch1（骨形態(tài)發(fā)生蛋白2-Delta樣配體4-Notch同源體1）信號(hào)通路的蛋白表達(dá)。 結(jié)果：QSG能改善心肌梗死大鼠的心功能，增加心臟血流量和心臟的微血管密度。體外研究表明，QSG能提高內(nèi)皮細(xì)胞的活力、促進(jìn)內(nèi)皮細(xì)胞遷移和成管能力。機(jī)制上，QSG能夠上調(diào)大鼠心臟梗死邊緣區(qū)域BMP2的表達(dá)，同時(shí)下調(diào)Dll4和Notch1的表達(dá)。在OGD誘導(dǎo)的內(nèi)皮損傷模型中，QSG有類似的作用。 結(jié)論：QSG可能通過調(diào)節(jié)BMP2-Dll4-Notch1通路促進(jìn)血管新生，對(duì)心肌梗死發(fā)揮保護(hù)作用。BMP2可能是治療IHD的潛在治療靶點(diǎn)。

    Abstract:
    Objective: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. Methods: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. Results: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. Conclusion: QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

    關(guān)鍵詞:
    血管新生;骨形態(tài)發(fā)生蛋白2;Delta樣配體4;心肌缺血;Notch同源體1;芪參顆粒

    Keywords:


    Project Supported:
    This work was supported by the National Natural Science Foundation of China held by LL (No. 81904169) and Excellent Youth Foundation of BUCM held by DG (No. BUCM-2019-JCRC005).

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