Popova T A, Muzyko E A, Kustova M V, Bychenkova M A, Perfilova V N, Prokofiev I I, Samoylova M A, Tyurenkov I N, Latypova G M, Kataev V A
Volgograd State Medical University, Volgograd, Russia.
Bashkir State Medical University, Ufa, Russia.
Biomed Khim. 2018 Aug;64(4):334-343. doi: 10.18097/PBMC20186404334.
Experimental chronic heart failure (CHF), caused by administration of L-isoproterenol (2.5 mg/kg twice a day intraperitoneally for 21 days), promotes uncoupling of respiration and oxidative phosphorylation. The rate of mitochondrial oxygen consumption in the metabolic state V3 by Chance in animals with CHF decreased by 53.3% (p<0.05) with malate using (as an oxidation substrate feeding сomplex I of the electron transport chain (ETC)), by 70.6% (p<0.05) with succinate using (сomplex II substrate) and by 63.6% (p<0.05) when malate and succinate were added simultaneously. The respiratory control ratio significantly decreased 2.3 times for сomplex I, 2.5 for сomplex II, and 2.6 times for the simultaneous operation of two respiratory chain complexes in mitochondria of CHF rats compared to intact animals. Mitochondrial dysfunction in experimental CHF is evidently due to the development of oxidative stress. It was revealed that the content of malonic dialdehyde (MDA) in the group of rats with experimental CHF was higher by 54.7% (p<0.05), as compared with intact animals. The activity of superoxide dismutase (SOD) and catalase was lower by 17.5% (p<0.05), and by 18.4%, respectively than in the intact group. The dense extract from herba of Primula veris L. (DEHPV) 30 mg/kg limits the development of mitochondrial dysfunction in rats with experimental CHF, as evidenced by an increase in the role of V3 respiration for the first and second respiratory chain complexes in 1.7 (p<0.05) and 2.0 times (p<0.05), respectively, the ratio of respiratory control (RCR) - 1.7 times (p<0.05) for сomplex I and 2 times (p<0.05) for сomplex II compared with the negative control. The concentration of MDA was by 15.7% (p<0.05), lower and the activity of SOD was by 56.3% (p<0.05) higher.
通过腹腔注射L-异丙肾上腺素（2.5毫克/千克，每天两次，共21天）诱导的实验性慢性心力衰竭（CHF），会促进呼吸与氧化磷酸化的解偶联。在CHF动物中，Chance法测得的代谢状态V3下线粒体氧消耗率，以苹果酸为底物（作为电子传递链（ETC）复合体I的氧化底物）时降低了53.3%（p<0.05），以琥珀酸为底物（复合体II底物）时降低了70.6%（p<0.05），同时添加苹果酸和琥珀酸时降低了63.6%（p<0.05）。与正常动物相比，CHF大鼠线粒体中复合体I的呼吸控制率显著降低了2.3倍，复合体II降低了2.5倍，两条呼吸链复合体同时运作时降低了2.6倍。实验性CHF中的线粒体功能障碍显然是由于氧化应激的发展所致。结果显示，实验性CHF大鼠组中的丙二醛（MDA）含量比正常动物高54.7%（p<0.05）。超氧化物歧化酶（SOD）和过氧化氢酶的活性分别比正常组低17.5%（p<0.05）和18.4%。报春花全草的浓缩提取物（DEHPV），剂量为30毫克/千克，可限制实验性CHF大鼠线粒体功能障碍的发展，这表现为第一和第二呼吸链复合体的V3呼吸作用分别增加了1.7倍（p<0.05）和2.0倍（p<0.05），呼吸控制率（RCR）与阴性对照组相比，复合体I增加了1.7倍（p<0.05），复合体II增加了2倍（p<0.05）。MDA浓度降低了15.7%（p<0.05），SOD活性提高了56.3%（p<0.05）。
