The present study was designed to investigate the therapeutic effects of injection of dihydroartemisinin (DHA) into the balloon-injured carotid arteries on balloon injury-induced neointimal formation and to explore whether autophagy is involved in the action of DHA. Percutaneous transluminal balloon angioplasty was performed in Sprague-Dawley rats to induce neointimal formation, immediately after which DHA (100 μmol/l × 1 ml) and/or Rapamycin (1 mg/100 μl), were injected into the balloon-injured carotid arteries. After 14 days, the serum samples and carotid artery tissues were harvested for analysis. Rat aortic vascular smooth muscle cells (VSMCs) were pretreated with DMSO (vehicle), DHA (1, 10, and 100 μmol/l), or 3-methyladenine (3-MA; 10 mM) for 1 h and then stimulated with platelet-derived growth factor-BB (PDGF-BB; 10 ng/ml) for another 24 h. Animal experiments showed that DHA attenuated the balloon injury-induced neointimal formation, inflammation and VSMC phenotypic transition by inhibiting the balloon injury-induced autophagy activation. In vitro results showed that DHA attenuated the PDGF-BB-induced VSMC phenotypic transition, proliferation, and migration by inhibiting the PDGF-BB-induced autophagy activation. Taken together, DHA ameliorates balloon injury-induced neointimal formation through suppressing autophagy. This study provides insights into the development of a drug-eluting stent using DHA.

中文翻译：

---

双氢青蒿素通过抑制血管平滑肌细胞自噬改善球囊损伤诱导的新生内膜形成

本研究旨在研究双氢青蒿素 (DHA) 注射到球囊损伤颈动脉对球囊损伤诱导的新生内膜形成的治疗效果，并探讨自噬是否参与 DHA 的作用。在 Sprague-Dawley 大鼠中进行经皮腔内球囊血管成形术以诱导新内膜形成，然后立即将 DHA（100 μmol/l × 1 ml）和/或雷帕霉素（1 mg/100 μl）注射到球囊损伤的颈动脉中. 14 天后，采集血清样品和颈动脉组织进行分析。大鼠主动脉血管平滑肌细胞 (VSMC) 用 DMSO（载体）、DHA（1、10 和 100 μmol/l）或 3-甲基腺嘌呤（3-MA；10 mM）预处理 1 小时，然后用血小板刺激-衍生生长因子-BB（PDGF-BB；10 ng/ml）再培养 24 小时。动物实验表明，DHA 通过抑制球囊损伤引起的自噬激活，减弱了球囊损伤引起的新内膜形成、炎症和 VSMC 表型转变。体外结果表明，DHA 通过抑制 PDGF-BB 诱导的自噬激活减弱了 PDGF-BB 诱导的 VSMC 表型转变、增殖和迁移。总之，DHA 通过抑制自噬来改善球囊损伤引起的新内膜形成。这项研究为使用 DHA 开发药物洗脱支架提供了见解。体外结果表明，DHA 通过抑制 PDGF-BB 诱导的自噬激活减弱了 PDGF-BB 诱导的 VSMC 表型转变、增殖和迁移。总之，DHA 通过抑制自噬来改善球囊损伤引起的新内膜形成。这项研究为使用 DHA 开发药物洗脱支架提供了见解。体外结果表明，DHA 通过抑制 PDGF-BB 诱导的自噬激活减弱了 PDGF-BB 诱导的 VSMC 表型转变、增殖和迁移。总之，DHA 通过抑制自噬来改善球囊损伤引起的新内膜形成。这项研究为使用 DHA 开发药物洗脱支架提供了见解。