Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang, China.
Basic Clin Pharmacol Toxicol. 2013 Feb;112(2):77-82. doi: 10.1111/j.1742-7843.2012.00933.x.
Epidemiological data have shown that methamphetamine (MA) abuse significantly increases the risk of developing pulmonary arterial hypertension (PAH). To investigate whether MA could induce PAH and its possible mechanism, rats were exposed daily to MA for 5 weeks in the absence or presence of fluoxetine. The results showed that the pulmonary arterial pressure was not significantly increased, but the pulmonary arterial remodelling was markedly developed in the MA exposure group. The protein expressions of the serotonin transporter (5-HTT) and 5-HT(1B) receptor were increased in the lungs and in the pulmonary arteries of MA-treated rats. Fluoxetine attenuated the pulmonary arterial remodelling and down-regulated the protein expression of 5-HTT and 5-HT(1B) receptor in pulmonary arteries of MA-treated rats. These findings suggest that fluoxetine has a novel potential suppressive effect on the chronic MA-induced pulmonary vascular remodelling and also suggest that 5-HTT and 5-HT(1B) receptor may be involved as part of its mechanism.
流行病学数据表明，甲基苯丙胺（MA）滥用显著增加了肺动脉高压（PAH）的发病风险。为了探讨 MA 是否会导致 PAH 及其可能的机制，研究人员将大鼠每天暴露于 MA 中，持续 5 周，同时或不给予氟西汀。结果表明，虽然肺动脉压没有显著升高，但 MA 暴露组的肺血管重构明显发展。在 MA 处理的大鼠肺部和肺动脉中，5-羟色胺转运体（5-HTT）和 5-羟色胺（1B）受体的蛋白表达增加。氟西汀减轻了 MA 处理大鼠的肺血管重构，并下调了 MA 处理大鼠肺动脉中 5-HTT 和 5-HT（1B）受体的蛋白表达。这些发现表明，氟西汀对慢性 MA 诱导的肺血管重构具有新的潜在抑制作用，并且 5-HTT 和 5-HT（1B）受体可能作为其机制的一部分参与其中。
