Kirova Yu I, Shakova F M, Germanova E L, Romanova G A, Voronina T A
Institute of General Pathology and Pathophysiology, Moscow, Russia.
Zakusov Research Institute of Pharmacology, Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2020;120(1):62-69. doi: 10.17116/jnevro202012001162.
To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats.
Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis.
It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug.
The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.
研究美西律对年轻和老年大鼠大脑中脑线粒体生成的诱导能力。
采用蛋白质免疫印迹分析，评估美西律（20、40、100mg/kg；20天；腹腔注射）对年轻（3个月）和老年（6、9、12和15个月）远交雄性大鼠大脑皮质中线粒体生成标记蛋白表达水平的影响。
首次表明，40和100mg/kg剂量的美西律连续注射可使年轻和老年远交雄性大鼠大脑皮质中的琥珀酸受体SUCNR1以及线粒体生物合成的蛋白质标记物呈剂量依赖性诱导：转录共激活因子PGC-1α、转录因子（NRF1、TFAM）、呼吸酶催化亚基（NDUV2、NDUV2、细胞色素b、COX2）和ATP合酶（ATP5A）。仅在药物疗程中观察到美西律依赖性线粒体酶亚基和PGC-1α的过表达。
结果表明美西律能够诱导年轻和老年动物的脑线粒体生成并消除线粒体功能障碍，从而对衰老和神经退行性疾病中疾病发展的关键发病机制之一产生影响。
