West China Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).
The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
Med Sci Monit. 2018 Nov 23;24:8459-8468. doi: 10.12659/MSM.911317.
BACKGROUND This study investigated the effect and the possible mechanism of trimetazidine in atherosclerosis. MATERIAL AND METHODS We established an atherosclerotic rat model by high-fat diet and vitamin D injection. Rats were separated into 3 different groups: control, atherosclerosis, and trimetazidine (n=10). The aortic artery was isolated and its morphological features were examined by hematoxylin and eosin (HE) staining. Serum low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), and triglycerides (TG) were analyzed using an automatic biochemical analyzer. Human aortic smooth muscle cells (HASMCs) were cultured and divided into 5 groups: no treatment, H₂O₂ treatment only, trimetazidine preincubation before H₂O₂ treatment, oxidized low-density lipoprotein (oxLDL) treatment only, and trimetazidine preincubation before oxLDL treatment. HASMCs proliferation was tested using the Cell Counting Kit-8. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity of the aortic artery, and HASMCs were measured using commercially available kits. RESULTS HE staining assay showed that trimetazidine suppressed the progression of atherosclerosis and reduced foam cell formation in the aortic artery without affecting serum lipid levels. HASMCs proliferation assay revealed that trimetazidine alleviated the inhibitory effect of H₂O₂ on HASMCs proliferation and inhibited oxLDL-induced proliferation of HASMCs. Moreover, trimetazidine ameliorated ROS up-regulation elicited by H₂O₂ or oxLDL in HASMCs. Additionally, trimetazidine restored SOD activity and reduced MDA content of HASMCs. CONCLUSIONS Trimetazidine suppressed the progression of atherosclerosis by enhancing energy value, decreasing ROS level of aortic artery, modulating HASMCs proliferation, and reducing oxidative stress in HASMCs.
本研究旨在探讨曲美他嗪在动脉粥样硬化中的作用及其可能的机制。
我们通过高脂饮食和维生素 D 注射建立了动脉粥样硬化大鼠模型。大鼠被分为 3 组：对照组、动脉粥样硬化组和曲美他嗪组（n=10）。分离大鼠的主动脉并进行苏木精和伊红（HE）染色，观察其形态特征。使用自动生化分析仪分析血清低密度脂蛋白胆固醇（LDL-c）、总胆固醇（TC）和甘油三酯（TG）。培养人主动脉平滑肌细胞（HASMCs），并将其分为 5 组：无处理组、H₂O₂处理组、H₂O₂处理前曲美他嗪孵育组、氧化型低密度脂蛋白（oxLDL）处理组和 oxLDL 处理前曲美他嗪孵育组。使用细胞计数试剂盒-8 检测 HASMCs 的增殖。使用市售试剂盒测量主动脉的活性氧（ROS）和丙二醛（MDA）水平、超氧化物歧化酶（SOD）活性以及 HASMCs 的 ROS 和 MDA 水平。
HE 染色结果表明，曲美他嗪抑制了动脉粥样硬化的进展，减少了主动脉泡沫细胞的形成，而不影响血清脂质水平。HASMCs 增殖试验表明，曲美他嗪减轻了 H₂O₂对 HASMCs 增殖的抑制作用，并抑制了 oxLDL 诱导的 HASMCs 增殖。此外，曲美他嗪改善了 H₂O₂或 oxLDL 引起的 HASMCs 中 ROS 的上调。此外，曲美他嗪恢复了 HASMCs 的 SOD 活性并降低了 MDA 含量。
曲美他嗪通过增强主动脉的能量值、降低 ROS 水平、调节 HASMCs 的增殖以及减轻 HASMCs 的氧化应激来抑制动脉粥样硬化的进展。
