Inflammation and the proliferation of vascular smooth muscle cells (VSMCs) are seen to play critical roles in the development of vascular complications induced by diabetes and hyperglycemia. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the effect of DHA on high glucose (HG)-induced inflammation and proliferation of VSMCs remains unknown. Therefore, this study aims to show that DHA significantly inhibited the proliferation of VSMCs and that expression of the inflammatory cytokines IL-1β and TNF-α was induced by HG in a dose-dependent manner. Additionally, we were able to determine that KLF15 played a critical role in HG-induced VSMC proliferation and inflammation, confirming its protective effects observed after DHA treatment in the HG-induced inflammatory response of VSMCs. DHA was observed to directly depress the HG-induced expression of miR-376b-3p, which targeted the 3′-UTR of KLF15 and inhibited its expression. These results suggested that DHA plays a protective role in HG-induced VSMC proliferation and associated inflammation by inhibiting the miR-376b-3p/KLF15 axis. Our findings provide new evidence of the mechanisms of DHA and its critical role in treating the pathogenesis of diabetic vascular complications.

炎症和血管平滑肌细胞 (VSMC) 的增殖被认为在糖尿病和高血糖引起的血管并发症的发展中起着关键作用。双氢青蒿素 (DHA) 已被确定为青蒿素的半合成衍生物，具有广泛的保护作用。然而，DHA 对高糖 (HG) 诱导的 VSMC 炎症和增殖的影响仍然未知。因此，本研究旨在表明 DHA 显着抑制 VSMC 的增殖，并且 HG 以剂量依赖性方式诱导炎性细胞因子 IL-1β 和 TNF-α 的表达。此外，我们能够确定 KLF15 在 HG 诱导的 VSMC 增殖和炎症中发挥了关键作用，证实了 DHA 处理后观察到的其在 HG 诱导的 VSMC 炎症反应中的保护作用。观察到 DHA 直接抑制 HG 诱导的 miR-376b-3p 表达，miR-376b-3p 靶向 KLF15 的 3'-UTR 并抑制其表达。这些结果表明，DHA 通过抑制 miR-376b-3p/KLF15 轴在 HG 诱导的 VSMC 增殖和相关炎症中发挥保护作用。我们的发现为 DHA 的机制及其在治疗糖尿病血管并发症发病机制中的关键作用提供了新证据。这些结果表明，DHA 通过抑制 miR-376b-3p/KLF15 轴在 HG 诱导的 VSMC 增殖和相关炎症中发挥保护作用。我们的发现为 DHA 的机制及其在治疗糖尿病血管并发症发病机制中的关键作用提供了新证据。这些结果表明，DHA 通过抑制 miR-376b-3p/KLF15 轴在 HG 诱导的 VSMC 增殖和相关炎症中发挥保护作用。我们的发现为 DHA 的机制及其在治疗糖尿病血管并发症发病机制中的关键作用提供了新证据。