人参皂苷Re通过调节miR-489/myd88/NF-κB通路抑制心肌纤维化。
Ginsenoside Re inhibits myocardial fibrosis by regulating miR-489/myd88/NF-κB pathway.
作者信息
Sun Jinghui, Wang Ru, Chao Tiantian, Peng Jun, Wang Chenglong, Chen Keji
机构信息
National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fujian, China.
出版信息
J Ginseng Res. 2023 Mar;47(2):218-227. doi: 10.1016/j.jgr.2021.11.009. Epub 2021 Dec 2.
BACKGROUND
Myocardial fibrosis (MF) is an advanced pathological manifestation of many cardiovascular diseases, which can induce heart failure and malignant arrhythmias. However, the current treatment of MF lacks specific drugs. Ginsenoside Re has anti-MF effect in rat, but its mechanism is still not clear. Therefore, we investigated the anti-MF effect of ginsenoside Re by constructing mouse acute myocardial infarction (AMI) model and AngⅡ induced cardiac fibroblasts (CFs) model.
METHODS
The anti-MF effect of miR-489 was investigated by transfection of miR-489 mimic and inhibitor in CFs. Effect of ginsenoside Re on MF and its related mechanisms were investigated by ultrasonographic, ELISA, histopathologic staining, transwell test, immunofluorescence, Western blot and qPCR in the mouse model of AMI and the AngⅡ-induced CFs model.
RESULTS
MiR-489 decreased the expression of α-SMA, collagenⅠ, collagen Ⅲ and myd88, and inhibited the phosphorylation of NF-κB p65 in normal CFs and CFs treated with AngⅡ. Ginsenoside Re could improve cardiac function, inhibit collagen deposition and CFs migration, promote the transcription of miR-489, and reduce the expression of myd88 and the phosphorylation of NF-κB p65.
CONCLUSION
MiR-489 can effectively inhibit the pathological process of MF, and the mechanism is at least partly related to the regulation of myd88/NF-κB pathway. Ginsenoside Re can ameliorate AMI and AngⅡ induced MF, and the mechanism is at least partially related to the regulation of miR-489/myd88/NF-κB signaling pathway. Therefore, miR-489 may be a potential target of anti-MF and ginsenoside Re may be an effective drug for the treatment of MF.
背景
心肌纤维化（MF）是许多心血管疾病的晚期病理表现，可诱发心力衰竭和恶性心律失常。然而，目前MF的治疗缺乏特效药物。人参皂苷Re对大鼠有抗MF作用，但其机制尚不清楚。因此，我们通过构建小鼠急性心肌梗死（AMI）模型和血管紧张素Ⅱ诱导的心脏成纤维细胞（CFs）模型，研究人参皂苷Re的抗MF作用。
方法
通过在CFs中转染miR-489模拟物和抑制剂来研究miR-489的抗MF作用。在AMI小鼠模型和血管紧张素Ⅱ诱导的CFs模型中，通过超声心动图、酶联免疫吸附测定、组织病理学染色、Transwell试验、免疫荧光、蛋白质免疫印迹法和定量聚合酶链反应，研究人参皂苷Re对MF及其相关机制的影响。
结果
miR-489降低正常CFs和血管紧张素Ⅱ处理的CFs中α-平滑肌肌动蛋白、Ⅰ型胶原、Ⅲ型胶原和髓样分化因子88（myd88）的表达，并抑制核因子κB（NF-κB）p65的磷酸化。人参皂苷Re可改善心脏功能，抑制胶原沉积和CFs迁移，促进miR-489的转录，并降低myd88的表达和NF-κB p65的磷酸化。
结论
miR-489可有效抑制MF的病理过程，其机制至少部分与myd88/NF-κB信号通路的调控有关。人参皂苷Re可改善AMI和血管紧张素Ⅱ诱导的MF，其机制至少部分与miR-489/myd88/NF-κB信号通路的调控有关。因此，miR-489可能是抗MF的潜在靶点，人参皂苷Re可能是治疗MF的有效药物。
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