Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
Department of Anesthesiology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine CSU, Zhuzhou Central Hospital, Zhuzhou, Hunan 412000, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11972. Epub 2021 Mar 24.
Atherosclerosis is a chronic vascular inflammatory disease, and is associated with oxidative stress and endothelial dysfunction. Homocysteine (HCY) can cause damage to endothelial cells via the enhancement of the endoplasmic reticulum stress (ERS) pathway. Propofol has a protective effect on endothelial injury and can suppress inflammation and oxidation. The purpose of the present study was to investigate the protective effect of propofol on HCY‑induced inflammation and apoptosis of human umbilical vein endothelial cells (HUVECs). HCY was used to establish the endothelial injury model. Cell Counting Kit‑8 assays and flow cytometry were used to detect cell viability and apoptosis, respectively. Then, ELISA was performed to examine the expression levels of inflammatory cytokines, and the expression levels of proteins related to inflammation, apoptosis and ERS were determined via western blotting. Results showed that propofol increased cell viability, suppressed NF‑κB signaling pathway activation and decreased the expression levels of inflammatory factors in HUVECs induced by HCY. Moreover, propofol could inhibit the expression of proteins involved in ERS, including ER chaperone BiP (Bip), C/EBP‑homologous protein, protein kinase R‑like ER kinase and inositol‑requiring 1α, and reduce cell apoptosis of HCY‑induced HUVECs. However, the overexpression of Bip could reactivate ERS and the NF‑κB signaling pathway, as well as promote inflammation and cell apoptosis, when compared with HCY‑treated groups. In conclusion, propofol can ameliorate inflammation and cell apoptosis of HUVECs induced by HCY via inhibiting ERS, which may provide a novel insight into the treatment of atherosclerosis.
动脉粥样硬化是一种慢性血管炎症性疾病，与氧化应激和内皮功能障碍有关。同型半胱氨酸（HCY）可通过增强内质网应激（ERS）途径对内皮细胞造成损伤。丙泊酚对内皮损伤具有保护作用，可抑制炎症和氧化。本研究旨在探讨丙泊酚对 HCY 诱导的人脐静脉内皮细胞（HUVEC）炎症和凋亡的保护作用。使用 HCY 建立内皮损伤模型。细胞计数试剂盒-8 检测和流式细胞术分别用于检测细胞活力和凋亡。然后，通过 ELISA 检测炎症细胞因子的表达水平，通过 Western blot 检测与炎症、凋亡和 ERS 相关的蛋白表达水平。结果表明，丙泊酚可增加细胞活力，抑制 HCY 诱导的 HUVEC 中 NF-κB 信号通路的激活，并降低炎症因子的表达水平。此外，丙泊酚可抑制 ERS 相关蛋白的表达，包括内质网伴侣 BiP（Bip）、C/EBP 同源蛋白、蛋白激酶 R 样内质网激酶和肌醇需求酶 1α，并减少 HCY 诱导的 HUVEC 细胞凋亡。然而，与 HCY 处理组相比，Bip 的过表达可重新激活 ERS 和 NF-κB 信号通路，并促进炎症和细胞凋亡。综上所述，丙泊酚通过抑制 ERS 可改善 HCY 诱导的 HUVEC 炎症和细胞凋亡，这可能为动脉粥样硬化的治疗提供新的思路。
