解毒活血汤通过 miRNA-126 激活血管内皮生长因子信号通路,促进受损血管的再内皮化。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY Biological & pharmaceutical bulletin Pub Date : 2024-04-20 DOI:10.1248/bpb.b23-00858
Zhiming Liu, Guangmie Xie, Zuwei Li, Hanbin Luo, Jianhong Zhou, Jie Cheng, Xiaolin Wang, Xiaoyan Huang, Guohui Zou
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引用次数: 0

摘要

支架内再狭窄(ISR)的发生给经皮冠状动脉介入治疗(PCI)带来了巨大挑战。因此,促进血管再内皮化对抑制内皮增生至关重要。在这项研究中,我们阐明了解毒活血化瘀汤(DABCD)通过 miRNA-126 介导的血管内皮生长因子(VEGF)信号通路调节促进血管再内皮化以避免 ISR 的机制。通过球囊损伤建立了大鼠PCI术后再狭窄模型。在模型建立 14 天和 28 天后收集损伤的主动脉段。我们的研究结果表明,在球囊损伤后的第 14 天和第 28 天,DABCD 可减少内膜增生和炎症,促进血管再内皮化。此外,DABCD 明显增加了大鼠血清中 NO 的表达,并显著减少了 ET-1 的产生。DABCD 还能提高血管组织中 eNOS 的 mRNA 水平以及 VEGF、p-Akt 和 p-ERK1/2 的蛋白表达。意想不到的是,气球损伤大鼠主动脉组织中 miR-126a-5p mRNA 的表达明显低于对照组大鼠主动脉组织,而 DABCD 组中的 miR-126a-5p 水平更高。本研究结果表明,DABCD 对动脉内膜损伤的血管再内皮化效应与抑制新内膜形成和增强血管内皮活性有关。更具体地说,DABCD 的作用至少部分是通过 miR-126 介导的血管内皮生长因子信号通路激活来介导的。
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Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.
The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased NO expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of eNOS and the protein expression of VEGF, p-Akt, and p-ERK1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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