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肾素-血管紧张素系统抑制剂、基质金属蛋白酶-9抑制剂和蛋白质激素对甲基苯丙胺诱导的神经毒性的可能修复机制。

Possible repair mechanisms of renin-angiotensin system inhibitors, matrix metalloproteinase-9 inhibitors and protein hormones on methamphetamine-induced neurotoxicity.

作者信息

Zhao Wei, Zhao Yuan-Ling, Liu Ming, Liu Lian, Wang Yun

机构信息

Department of Drug Control, Criminal Investigation Police University of China, Shenyang, 110854, Liaoning, People's Republic of China.

Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, People's Republic of China.

出版信息

Mol Biol Rep. 2021 Nov;48(11):7509-7516. doi: 10.1007/s11033-021-06741-y. Epub 2021 Oct 8.

Abstract

Methamphetamine is a highly addictive central stimulant with extensive and strong neurotoxicity. The neurotoxicity of methamphetamine is closely related to the imbalance of dopamine levels and the destruction of the blood-brain barrier. An increase in dopamine may induce adverse effects such as behavioral sensitization and excessive locomotion. Damage to the blood-brain barrier can cause toxic or harmful substances to leak to the central nervous system, leading to neurotoxicity. The renin-angiotensin system is essential for the regulation of dopamine levels in the brain. Matrix metalloproteinase-9 causes reward effects and behavioral sensitization by inducing dopamine release. Prolactin has been shown to be involved in the regulation of tight junction proteins and the integrity of the blood-brain barrier. At present, the treatment of methamphetamine detoxification is still based on psychotherapy, and there is no specific medicine. With the rapid increase in global seizures of methamphetamine, the treatment of its toxicity has attracted more and more attention. This review intends to summarize the therapeutic mechanisms of renin-angiotensin inhibitors, matrix metalloproteinase-9 inhibitors and protein hormones (prolactin) on methamphetamine neurotoxicity. The repair effects of these three on methamphetamine may be related to the maintenance of brain dopamine balance and the integrity of the blood-brain barrier. This review is expected to provide the new therapeutic strategy of methamphetamine toxicity.

摘要

甲基苯丙胺是一种极易成瘾的中枢兴奋剂,具有广泛而强烈的神经毒性。甲基苯丙胺的神经毒性与多巴胺水平失衡及血脑屏障破坏密切相关。多巴胺增加可能诱发行为敏化和过度运动等不良反应。血脑屏障受损会导致有毒有害物质渗漏至中枢神经系统,引发神经毒性。肾素 - 血管紧张素系统对大脑中多巴胺水平的调节至关重要。基质金属蛋白酶 -9 通过诱导多巴胺释放产生奖赏效应和行为敏化。催乳素已被证明参与紧密连接蛋白的调节及血脑屏障的完整性。目前,甲基苯丙胺脱毒治疗仍以心理治疗为主,尚无特效药物。随着全球甲基苯丙胺缉获量的迅速增加,其毒性治疗受到越来越多的关注。本综述旨在总结肾素 - 血管紧张素抑制剂、基质金属蛋白酶 -9 抑制剂和蛋白质激素(催乳素)对甲基苯丙胺神经毒性的治疗机制。这三者对甲基苯丙胺的修复作用可能与维持脑多巴胺平衡及血脑屏障的完整性有关。本综述有望为甲基苯丙胺毒性提供新的治疗策略。

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