Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Zhong Road, Shanghai, 200072, China.
Department of Cardio-Thoracic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Zhong Road, Shanghai, 200072, China.
Lipids Health Dis. 2017 Oct 10;16(1):198. doi: 10.1186/s12944-017-0582-7.
Foam cell formation and apoptosis are closely associated with atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in THP1 human acute monocytic leukemia cells and investigated the associated molecular mechanisms.
THP1-derived macrophages were incubated with salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell formation. Cytotoxicity, lipid deposition, apoptosis, and the expression of various proteins were tested using the CCK8 kit, Oil Red O staining, flow cytometry, and western blotting, respectively.
Ox-LDL treatment alone promoted macrophage-derived foam cell formation, while salidroside treatment alone inhibited it (p < 0.05). The number of early/late apoptotic cells decreased with salidroside treatment in a dose-dependent manner (p < 0.05). Salidroside dramatically upregulated nuclear factor erythroid 2-related factor 2, but had no effect on heme oxygenase-1 expression; moreover, it markedly downregulated ox-LDL receptor 1 and upregulated ATP-binding cassette transporter A1. Salidroside also obviously decreased the phosphorylation of JNK, ERK, p38 MAPK, and increased that of Akt. However, the total expression of these proteins was not affected.
Based on our findings, we speculate that salidroside can suppress ox-LDL-induced THP1-derived foam cell formation and apoptosis, partly by regulating the MAPK and Akt signaling pathways.
泡沫细胞的形成和凋亡与动脉粥样硬化的发病机制密切相关。本研究旨在探讨红景天苷对氧化型低密度脂蛋白（ox-LDL）诱导的 THP1 人急性单核白血病细胞源性泡沫细胞形成和凋亡的影响，并探讨其相关的分子机制。
用红景天苷孵育 THP1 源性巨噬细胞 5 h 后，再用 ox-LDL 孵育 24 h 诱导泡沫细胞形成。采用 CCK8 试剂盒、油红 O 染色、流式细胞术和 Western blot 分别检测细胞毒性、脂质沉积、凋亡和各种蛋白的表达。
ox-LDL 处理可促进巨噬细胞源性泡沫细胞形成，而红景天苷处理则抑制其形成（p<0.05）。红景天苷呈剂量依赖性地减少早期/晚期凋亡细胞的数量（p<0.05）。红景天苷显著上调核因子红细胞 2 相关因子 2（Nrf2）的表达，但对血红素加氧酶 1（HO-1）的表达无影响；此外，它还明显下调 ox-LDL 受体 1（LOX-1）的表达，上调三磷酸腺苷结合盒转运体 A1（ABCA1）的表达。红景天苷还明显降低 JNK、ERK、p38 MAPK 的磷酸化水平，增加 Akt 的磷酸化水平。然而，这些蛋白的总表达没有受到影响。
根据我们的研究结果，我们推测红景天苷可以抑制 ox-LDL 诱导的 THP1 源性泡沫细胞形成和凋亡，这可能部分是通过调节 MAPK 和 Akt 信号通路实现的。
