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应激条件下甲基苯丙胺的心脏毒性:单次剂量与长期使用的比较。

Cardiotoxicity of methamphetamine under stress conditions: comparison of single dose and long-term use.

机构信息

Department of Medical Toxicology, Kawasaki Medical School, Kurashiki 701‑0192, Japan.

出版信息

Mol Med Rep. 2013 Jun;7(6):1786-90. doi: 10.3892/mmr.2013.1408. Epub 2013 Apr 2.

Abstract

Methamphetamine (METH) abuse continues to be a worldwide problem, damaging the myocardial tissues, as well as the brains of individual users. In addition, stressors that increase drug cravings also contribute to cardiovascular diseases. The aim of the present study was to examine the myocardial effects of METH, including METH‑stress interactions and particularly, the effect of METH RNA expression in the heart. The study also aimed to compare single dose (acute) and long-term (chronic) treatments. Mice were divided into the control (C), METH injection (M), stress exposure (S) and METH plus stress (MS) groups and subjected to an acute water‑immersion restraint stress or a mixed chronic stress composed of restraint, electric foot‑shock and temperature change. METH was injected at 30 mg/kg (the acute study) or 10 mg/kg intraperitoneally (i.p.) three times per week (the chronic study). The results demonstrated that METH induced more deleterious effects in the myocardial tissues during acute and chronic administrations when under stress conditions. Heat shock proteins (Hsps) played a critical role in the acute phase, while numerous genes, including anti‑oxidant, anti‑apoptotic and physiological function genes, played significant roles in the chronic phase. These results indicate that METH abuse, ranging from episodes of binge abuse to chronic abuse over several years, may cause severe myocardial damage in human users under stress.

摘要

标题:METH 诱导的心肌损伤及其与应激的关系

摘要:冰毒(METH)滥用仍是一个全球性问题,不仅会损害个体使用者的心肌组织和大脑,还会增加药物成瘾的应激源,进而导致心血管疾病。本研究旨在探讨 METH 对心肌的影响,包括 METH-应激相互作用,特别是 METH 对心脏 RNA 表达的影响。本研究还比较了单次(急性)和长期(慢性)治疗的效果。将小鼠分为对照组(C)、METH 注射组(M)、应激暴露组(S)和 METH 加应激组(MS),并进行急性水浸束缚应激或混合慢性应激(由束缚、电击足底和温度变化组成)。METH 以 30mg/kg(急性研究)或 10mg/kg 腹腔注射(ip)的剂量,每周三次进行急性和慢性给药。结果表明,在应激条件下,METH 在急性和慢性给药时对心肌组织产生了更严重的损伤。热休克蛋白(Hsps)在急性期发挥关键作用,而在慢性期,许多基因,包括抗氧化、抗凋亡和生理功能基因,发挥了重要作用。这些结果表明,从狂欢性滥用到多年的慢性滥用,METH 滥用可能会导致人类使用者在应激下发生严重的心肌损伤。

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