| 引用本文:王咏1，2，王悠草1，王丽丽1，马度芳1，李晓1，3.黄芪协同红花-葶苈子抑制内皮细胞旁分泌改善心肌纤维化机制[J].世界中医药,2025,(03):. |
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| 黄芪协同红花-葶苈子抑制内皮细胞旁分泌改善心肌纤维化机制 |
| Mechanism of Astragali Radix and Carthami Flos-lepidii Semen in Synergistically Improving Myocardial Fibrosis by Inhibiting the Paracrine Effect of Cardiac Endothelial Cells |
| 投稿时间：2024-05-28 |
| DOI：10.3969/j.issn.1673-7202.2025.03.011 |
| 中文关键词: 心肌纤维化 内皮细胞间充质转化 旁分泌 黄芪 红花-葶苈子药对 转化生长因子-β1/Snail通路 协同 成纤维细胞 心脏微血管内皮细胞 |
| English Keywords:Myocardial fibrosis Endothelial-mesenchymal transition Paracrine Astragali Radix Carthami Flos and Lepidii Semen TGF-β1/Snail pathway Synergistically Cardiac fibroblast Cardiac microvascular endothelial cell |
| 基金项目:国家自然科学基金青年科学基金项目（82104797）；山东省自然科学基金青年项目（ZR2020QH333）；山东省济南市科技计划项目（202225004） |
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| 中文摘要: |
| 目的：观察黄芪协同红花-葶苈子抑制心肌纤维化的作用及机制。方法：结扎前降支制备心肌梗死后心力衰竭大鼠，红花-葶苈子（C-L）、黄芪（HR）与黄芪-红花-葶苈子（A-C-L）干预，马松染色检测纤维化程度，蛋白质印迹法检测血管性血友病因子（νWF）和α-平滑肌肌动蛋白（α-SMA），蛋白质印迹法及反转录聚合酶链式反应（RT-PCR）检测转化生长因子-β1（TGF-β1）、蜗牛家族转录抑制因子1（Snail）。构建缺氧心脏微血管内皮细胞（HCMEC），C-L、HR及A-C-L含药血清干预，免疫荧光（IF）检测血小板内皮细胞黏附分子（CD31）和α-SMA。A-C-L含药血清联合TGF-β1激活剂（SRI-011381）干预HCMEC，IF观察内皮细胞间充质转化，蛋白质印迹法和RT-PCR检测TGF-β1/Snail表达。提取HCMEC上清液干预心脏成纤维细胞（CF），酶联免疫吸附试验法（ELISA）检测上清液结缔组织生长因子（CTGF），检测CF增殖及胶原合成。结果：A-C-L抑制心力衰竭大鼠心肌纤维化效果最佳。C-L、HR及A-C-L均上调心力衰竭大鼠心肌和缺氧内皮细胞CD31、vWF及下调α-SMA表达，又以A-C-L效果最佳。联合应用SRI-011381后A-C-L抑制内皮间充质转化作用减弱。A-C-L抑制HCMEC中TGF-β1/Snail表达、下调CTGF分泌。提取A-C-L干预的HCMEC上清液培养CF，其CF活化和胶原合成低于HCMEC上清液培养的CF。结论：黄芪协同红花-葶苈子抑制心肌纤维化，其机制，抑制内皮间充质转化，下调内皮细胞中TGF-β1/Snail，以旁分泌方式抑制成纤维细胞增殖和胶原合成。 |
| English Summary: |
| To investigate the inhibitory effect and mechanism of Astragali Radix(AR) in combination with Carthami Flos-Lepidii Semen(C-L) on myocardial fibrosis.Methods:A rat model of heart failure following myocardial infarction was established by ligation of the left anterior descending coronary artery.The rats were treated with C-L，AR，or Astragali Radix-Carthami Flos-Lepidii Semen(A-C-L).Myocardial fibrosis was assessed using Masson's staining.The expression levels of von Willebrand factor(vWF) and α-smooth muscle actin(α-SMA) were detected by Western blot(WB)，while the expression of transforming growth factor-β1(TGF-β1) and Snail family transcriptional repressor 1(Snail) was analyzed using WB and reverse transcription-polymerase chain reaction(RT-PCR).A hypoxic cardiac microvascular endothelial cell(HCMEC) model was constructed，and HCMECs were treated with drug-containing serum from C-L，AR，or A-C-L.The expression of platelet endothelial cell adhesion molecule-1(CD31) and α-SMA was detected by immunofluorescence(IF).To further explore the mechanism of A-C-L in inhibiting endothelial-mesenchymal transition(EMT)，HCMECs were co-treated with A-C-L drug-containing serum and the TGF-β1 activator SRI-011381.EMT was assessed via IF，and TGF-β1/Snail expression was detected by WB and RT-PCR.To investigate the paracrine effect，the supernatant from HCMECs was collected and used to treat cardiac fibroblasts(CFs).The levels of connective tissue growth factor(CTGF) in the supernatant were measured by enzyme-linked immunosorbent assay(ELISA)，while CF proliferation and collagen synthesis were assessed.Results:A-C-L exhibited the most significant inhibitory effect on myocardial fibrosis in rats with heart failure.C-L，AR，and A-C-L upregulated CD31 and vWF expression while downregulating α-SMA in both myocardial tissue and hypoxic endothelial cells，with A-C-L demonstrating the strongest effect.After co-treatment with SRI-011381，the inhibitory effect of A-C-L on EMT was weakened.A-C-L inhibited the expression of the TGF-β1/Snail pathway and reduced CTGF secretion in HCMECs.CFs cultured with supernatant from A-C-L-treated HCMECs exhibited lower activation and collagen synthesis compared to those cultured with untreated HCMEC supernatant.Conclusion:AR combined with C-L inhibits myocardial fibrosis by suppressing EMT，downregulating TGF-β1/Snail expression in endothelial cells，and inhibiting fibroblast proliferation and collagen synthesis via a paracrine mechanism. |
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