The present study aimed to explore the effects of shikonin (SKN) on the damage of human venous endothelial cells (HUVECs) induced by ox-LDL and the underlying molecular mechanism. The HUVECs were randomly divided into six groups: control, ox-LDL, SKN + ox-LDL, SKN + ox-LDL + compound C, SKN + ox-LDL + si-Nrf2, and SKN + ox-LDL + si-HO-1. The MTT method was used to detect cell viability, flow cytometry was used to detect cell apoptosis and reactive oxygen species (ROS) levels, and Western blot was used to detect protein levels. Compared to the control group, the cell viability of the ox-LDL group decreased, the apoptosis rate increased, the level of cleaved caspase-3 was upregulated, and the level of Bcl-2 protein was downregulated. The level of TNF-α, IL-1β, IL-6, vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), and E-selectin (E-sel) was increased, ROS levels increased, and superoxide dismutase (SOD) level decreased. Moreover, the protein levels of p-AMPK, Nrf2, and HO-1 were decreased. Compared to the ox-LDL group, SKN treatment improves cell viability, alleviates cell apoptosis and oxidative stress injury, and upregulates the protein levels of p-AMPK, Nrf2, and HO-1. Compound C, si-Nrf2, and si-HO-1 administration inhibits the AMPK/Nrf2/HO-1 signaling pathway, increases ROS generation, and inhibits the antagonistic effect of SKN on ox-LDL-induced HUVECs damage. In summary, SKN suppressed ox-LDL-induced ROS production and improved cell viability and cell apoptosis via the AMPK/Nrf2/HO-1 pathway.

中文翻译：

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Shikonin 通过 AMPK/Nrf2/HO-1 信号通路减轻 ox-LDL 诱导的内皮细胞损伤

本研究旨在探讨紫草素（SKN）对ox-LDL诱导的人静脉内皮细胞（HUVECs）损伤的影响及其潜在分子机制。HUVEC 随机分为六组：对照、ox-LDL、SKN + ox-LDL、SKN + ox-LDL + 化合物 C、SKN + ox-LDL + si-Nrf2 和 SKN + ox-LDL + si-HO -1. MTT法检测细胞活力，流式细胞术检测细胞凋亡和活性氧（ROS）水平，Western blot检测蛋白水平。与对照组相比，ox-LDL组细胞活力降低，细胞凋亡率增加，cleaved caspase-3水平上调，Bcl-2蛋白水平下调。TNF-α的水平α，IL-1 β、IL-6、血管细胞粘附分子-1（VCAM1）、细胞间粘附分子-1（ICAM1）和E-选择素（E-sel）增加，ROS水平增加，超氧化物歧化酶（SOD）水平降低。此外，p-AMPK、Nrf2 和 HO-1 的蛋白质水平降低。与 ox-LDL 组相比，SKN 治疗提高了细胞活力，减轻了细胞凋亡和氧化应激损伤，并上调了 p-AMPK、Nrf2 和 HO-1 的蛋白质水平。化合物 C、si-Nrf2 和 si-HO-1 给药抑制 AMPK/Nrf2/HO-1 信号通路，增加 ROS 的产生，并抑制 SKN 对 ox-LDL 诱导的 HUVECs 损伤的拮抗作用。总之，SKN 通过 AMPK/Nrf2/HO-1 通路抑制 ox-LDL 诱导的 ROS 产生并改善细胞活力和细胞凋亡。