关于σ受体激动剂抗焦虑药盐酸法莫替唑（阿伏唑嗪）心脏保护作用的机制

On the Mechanism of the Cardioprotective Action of σ Receptor Agonist Anxiolytic Fabomotizole Hydrochloride (Afobazole).

作者信息

Kryzhanovskii S A, Kozhevnikova L M, Tsorin I B, Sukhanova I F, Ionova E O, Stolyaruk V N, Vititnova M B, Miroshkina I A, Seredenin S B

机构信息

V. V. Zakusov Research Institute of Pharmacology, Russian Academy of Sciences, Moscow, Russia.

Research Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2018 Sep;165(5):660-664. doi: 10.1007/s10517-018-4236-1. Epub 2018 Sep 17.

DOI:10.1007/s10517-018-4236-1

PMID:30225699

Abstract

Original translational rat model of chronic heart failure provoked by experimental anterior transmural myocardium infarction was employed to examine the preventive action of anxiolytic Afobazole (15 mg/kg/day administered intraperitoneally during the first 15 days after coronary occlusion) on the development of the heart failure assessed in 3 months after infarction. Afobazole prevented the development of pathologic remodeling of the myocardium, maintained its inotropic function, and decreased the plasma level of brain natriuretic peptide known as a biochemical marker of chronic heart failure. In the myocardium, Afobazole down-regulated overexpression of the genes induced in chronic heart failure and assessed by corresponding RNA levels, which code angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as well as Epac2 protein. The revealed biochemical changes are consistent with the data on cardioprotective action of Afobazole.

摘要

采用实验性前壁透壁心肌梗死诱发的慢性心力衰竭的原代翻译大鼠模型，以检验抗焦虑药阿福唑（在冠状动脉闭塞后的前15天内，每天腹腔注射15mg/kg）对梗死后3个月评估的心力衰竭发展的预防作用。阿福唑可预防心肌病理重塑的发展，维持其正性肌力功能，并降低作为慢性心力衰竭生化标志物的脑钠肽血浆水平。在心肌中，阿福唑下调了慢性心力衰竭中诱导的基因的过表达，并通过相应的RNA水平进行评估，这些基因编码血管紧张素（AT1A-R）、血管加压素（V1A-R）和糖皮质激素（GR）受体以及Epac2蛋白。所揭示的生化变化与阿福唑的心脏保护作用数据一致。