Effect of methamphetamine exposure on the plasma levels of endothelial-derived microparticles
Effect of methamphetamine exposure on the plasma levels of endothelial-derived microparticles
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DOI：
10.1016/j.drugalcdep.2018.02.015
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发表时间：
2018-05-01
影响因子：
4.2
通讯作者：
Hosseinzadeh, Soheila
中科院分区：
文献类型：
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作者：
Nazari, Azadeh;Zahmatkesh, Maryam;Hosseinzadeh, Soheila
背景：甲基苯丙胺(Meth)是一种神经毒素，可引起炎症、氧化应激，并引发内皮功能障碍和心血管疾病，是Meth使用障碍患者的第二大死亡原因。氧化应激和炎症引发了微粒(MP)的释放。这些是从细胞表面提取并在生物液中鉴定的细胞外小泡。MP水平在病理条件下发生变化，提示其潜在的生物标志物作用。在这方面，我们设计了本实验来研究Meth对血浆内皮源性微粒(EMP)水平的影响。分别于培养1、7、14d用细胞表面标志物AnnexinV、CD144、CD31、CD41a用流式细胞仪检测血浆EMPs水平。结果：冰毒增加了大鼠的运动活性(甲硫氨酸-1,277.12+/-20.17；甲硫氨酸-7,262.25+/-11.95；甲硫氨酸-14,265.75+/-14.75)，炎症和氧化指标，表现为C-反应蛋白的升高(甲硫氨酸-7，39.4+/-1.24；丙二醛(Meth-7，9.74+/-1.38；Meth-14，14.6+/-1.45，VS 4.43+/-0.32nmol/L)。我们还发现，与对照组相比，Meth暴露引发了内皮损伤，表现为EMP水平的升高(Meth-7，4.77+/-0.22；Meth-14，5.91+/-0.34，%Total Events/mL)。结论：Meth暴露刺激炎症和氧化途径，促进EMPs的脱落。检测EMPs水平可作为监测药物使用障碍患者内皮功能障碍的潜在诊断指标。
Background: 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 extra cellular 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).Methods: 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.Results: 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.Conclusion: 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.