Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Cognitive and Behavioral Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Drug Alcohol Depend. 2018 May 1;186:219-225. doi: 10.1016/j.drugalcdep.2018.02.015. Epub 2018 Mar 27.
Methamphetamine (Meth), a neurotoxin, induces inflammation, oxidative stress, and triggers endothelial dysfunction and cardiovascular disease which is the second cause of death among individuals with Meth-use disorder. Oxidative stress and inflammation trigger the microparticle (MP) release. These are extracellular vesicles extracted from cell surface and identified in biological fluids. MP levels alter during pathological conditions, suggesting its potential biomarker role. In this respect, we designed the present experiment to investigate the effects of Meth on the plasma level of the endothelial-derived microparticle (EMP).
Animals received Meth (4 mg/kg i.p.) for 1, 7 and 14 days and then, the plasma level of EMPs was evaluated, using cell surface markers, including AnnexinV, CD144, CD31, CD41a antigens with the flow cytometry method. The biochemical indices and locomotor activity were also assessed in a rat model.
Meth increased locomotor activity (Meth-1, 277.12 ± 20.17; Meth-7, 262.25 ± 11.95; Meth-14, 265.75 ± 14.75), inflammatory and oxidative indices as evidenced by rising of the C-reactive protein (Meth-7, 39.4 ± 1.24; Meth-14, 38.58 ± 2.19, vs 8.65 ± 0.45, mg/L) and malondialdehyde (Meth-7, 9.74 ± 1.38; Meth-14, 14.6 ± 1.45, vs 4.43 ± 0.32 nmol/L) plasma levels. We also found that Meth triggered endothelial injury, as demonstrated by elevated levels of EMP (Meth-7, 4.77 ± 0.22; Meth-14, 5.91 ± 0.34, % total events/mL) compared with control group.
Our data showed that Meth exposure stimulates inflammatory and oxidative pathways and facilitates the EMPs shedding. Measuring the level of EMPs might be applied as a potential diagnostic index to monitor the endothelial dysfunction in substance-use disorders.
甲基苯丙胺（Meth）是一种神经毒素，可引发炎症、氧化应激，并触发内皮功能障碍和心血管疾病，这是 Meth 使用障碍患者的第二大致死原因。氧化应激和炎症会触发微粒（MP）释放。这些是从细胞表面提取并在生物体液中鉴定出的细胞外囊泡。在病理条件下，MP 水平会发生变化，提示其可能具有生物标志物作用。在这方面，我们设计了本实验来研究 Meth 对血浆中内皮衍生微粒（EMP）水平的影响。
动物接受 4mg/kg i.p. 的 Meth 治疗 1、7 和 14 天，然后使用流式细胞术方法评估 EMP 的细胞表面标志物，包括 AnnexinV、CD144、CD31、CD41a 抗原，来评估血浆中 EMP 的水平。还在大鼠模型中评估了生化指标和运动活动。
Meth 增加了运动活动（Meth-1：277.12±20.17；Meth-7：262.25±11.95；Meth-14：265.75±14.75），炎症和氧化指数也随之上升，表现为 C 反应蛋白（Meth-7：39.4±1.24；Meth-14：38.58±2.19，vs 8.65±0.45，mg/L）和丙二醛（Meth-7：9.74±1.38；Meth-14：14.6±1.45，vs 4.43±0.32 nmol/L）血浆水平升高。我们还发现，Meth 引发了内皮损伤，表现为 EMP 水平升高（Meth-7：4.77±0.22；Meth-14：5.91±0.34，%总事件/mL）与对照组相比。
我们的数据表明，Meth 暴露刺激了炎症和氧化途径，并促进了 EMP 的脱落。测量 EMP 水平可能作为监测物质使用障碍患者内皮功能障碍的潜在诊断指标。
