Fedorova T N, Gusakov V S, Devyatov A A, Muzichuk O A, Lopachev A V, Belousova M A, Stvolinskii S L, Povarova O V, Gulyaev M V, Medvedev O S, Tutelyan V A
Research Center of Neurology, Moscow, Russia.
Lomonosov Moscow State University, Moscow, Russia.
Biomed Khim. 2020 Feb;66(2):145-150. doi: 10.18097/PBMC20206602145.
Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.
缺血性中风是社会上最重要的疾病之一，其特征是脑循环受损，伴有脑组织局灶性损伤和功能下降。尽管现代药理学取得了成功，但中风的药物治疗可能性仍然有限，研发具有神经保护作用、可防止脑细胞死亡的新药仍具有现实意义。在本研究中，我们研究了泛醇作为创新剂型的一部分，在不可逆24小时脑缺血大鼠模型上的神经保护活性，并评估了其神经保护作用的机制。在不可逆24小时局灶性脑缺血急性期静脉注射泛醇（30毫克/千克）具有直接神经保护作用，其特征是脑组织坏死体积减小。泛醇的保护作用归因于其通过直接抗自由基作用抑制氧化应激发展的能力，可防止坏死灶周围脑组织中脂质氢过氧化物含量增加，在实验动物大脑和血液中总抗氧化活性增加的情况下降低血浆中的脂质氧化速率。体外实验表明，泛醇能够在大鼠脑原代培养神经元4小时氧/葡萄糖剥夺后再进行20小时复氧的情况下防止细胞死亡。
