广州医科大学代小艳小组发现，去氢紫堇碱通过上调Spta1维持血管平滑肌细胞的收缩表型。该项研究成果于2025年1月20日在线发表在《中国药理学报》杂志上。

研究人员表示，血管平滑肌细胞（VSMC）表型转变在动脉粥样硬化的启动和进展中起着至关重要的作用。去氢紫堇碱（DHC）是传统中药川芎的主要活性成分，具有多种药理作用。然而，其对VSMC的影响尚不清楚。

研究人员旨在探讨DHC在VSMC表型转变中的作用及其潜在机制。研究发现，DHC以时间和剂量依赖的方式增加了大鼠VSMC收缩表型标志物的mRNA和蛋白质水平，如调宁蛋白1（Cnn1）、肌球蛋白重链（Myh11, SM-MHC）、平滑肌22α（Sm22α）和α-平滑肌肌动蛋白（Acta2, α-SMA）。此外，DHC抑制了血小板衍生生长因子BB（PDGF-BB）诱导的VSMC增殖和迁移。

在Apoe^−/−小鼠中，DHC治疗减少了颈动脉斑块面积和巨噬细胞浸润，同时增加了收缩表型标志物的表达。RNA测序分析揭示了DHC处理的大鼠VSMC中红细胞膜蛋白1（Spta1）的显著上调。值得注意的是，Spta1敲低有效地抑制了DHC最初促进的VSMC收缩表型标志物表达的增加。因此，DHC通过Spta1维持VSMC的收缩表型，从而减轻Apoe^−/−小鼠颈动脉的动脉粥样硬化斑块。

这项研究提供了支持中药，特别是含有DHC的川芎，作为治疗动脉粥样硬化性心血管疾病潜力的证据，从而扩展了这类草药的临床应用。

附：英文原文

Title: Dehydrocorydaline maintains the vascular smooth muscle cell contractile phenotype by upregulating Spta1

Author: Dang, Yuan-ye, Chen, Cui, Wei, Qiu-fen, Gao, Li-feng, Zhang, Shun-chi, Li, Yong-xian, Dai, Xiao-yan

Issue&Volume: 2025-01-20

Abstract: Vascular smooth muscle cell (VSMC) phenotypic switching plays a crucial role in the initiation and progression of atherosclerosis. Dehydrocorydaline (DHC), a major active component of the traditional Chinese herbal medicine Rhizoma Corydalis, exhibits diverse pharmacological effects. However, its impact on VSMCs remains largely unknown. This study aims to investigate the effects and underlying mechanisms of DHC in phenotypic switching of VSMCs. Our study revealed that DHC increased the mRNA and protein levels of rat VSMC contractile phenotype markers, such as calponin 1 (Cnn1), myosin heavy chain (Myh11, SM-MHC), smooth muscle 22α (Sm22α), and alpha-smooth muscle actin (Acta2, α-SMA) in a time- and dose-dependent manner. Additionally, DHC inhibited platelet-derived growth factor-BB-induced VSMC proliferation and migration. In Apoe/ mice, DHC treatment resulted in reduced carotid plaque areas and macrophage infiltration, along with increased contractile phenotype marker expression. RNA sequencing analysis revealed a significant upregulation of spectrin alpha, erythrocytic 1 (Spta1) in DHC-treated rat VSMCs. Strikingly, Spta1 knockdown effectively negated the increase in contractile phenotype marker expression in VSMCs that was initially prompted by DHC. Therefore, DHC preserves the VSMC contractile phenotype through Spta1, thereby attenuating carotid artery atherosclerotic plaques in Apoe/ mice. This study provides evidence supporting the potential use of Chinese herbal medicines, particularly those containing DHC such as Rhizoma Corydalis, in the treatment of atherosclerotic cardiovascular disease, thus expanding the clinical application of such herbal remedies.

DOI: 10.1038/s41401-024-01464-9

Source: https://www.nature.com/articles/s41401-024-01464-9