[姜黄素对阿霉素诱导氧化应激的心肌细胞线粒体功能的影响]

[EFFECT OF CURCUMIN ON MITOCHONDRIAL FUNCTION OF CARDIOMYOCYTES WITH DOXORUBICIN-INDUCED OXIDATIVE STRESS].

作者信息

Linnik O, Gonchar O, Nosar V, Drevytska T, Kovalyov O, Mankovska I

出版信息

Fiziol Zh (1994). 2017;63(1):10-16. doi: 10.15407/fz63.01.010.

DOI:10.15407/fz63.01.010

Abstract

We studied the effect of curcumin on the cardiomyocytes viability, processes of oxidative phosphorylation in the mitochondria of cardiomyocytes, their pro- and antioxidant balance in doxorubicin-induced oxidative stress. It has been revealed that administration of doxorubicin to rats led to a significant increase in the secondary products of lipid peroxidation (TBARS) in mitochondria by 21 and H(2)0(2) by 76%, reduction of the enzymatic activity of mitochondrial Mn-SOD by 14% and intensified catalase activity by 80% compared with the control. After combined use of doxorubicin and curcumin the content of TBARS and H(2)0(2) increased by 14 and 26%, respectively, the enzymatic activity of catalase decreased by 28%, and mitochondrial Mn-SOD activity intensified by 9%. During the incubation with doxorubicin, the number of live cells decreased by 30.4% and the number of necrotic cells increased by 30.4% relative to control. Coadministration of doxorubicin and curcumin led to augmented cell viability by 8%, while the number of necrotic cells reduced by 8% compared with the use of doxorubicin only. In assessing the parameters of mitochondrial respiration in rats that received injections of doxorubicin active breathing index (V(3)) fell by 43.8%, the oxidation rate of the contingency of phosphorylation (V(3)/V(4)(ATp)) decreased by 47% and phosphorylation efficiency index (ADP/O) also declined by 31.7% respectively compared with the control. The combined use of doxorubicin and curcumin improved the indicators of mitochondrial respiration compared to using only doxorubicin: V(3) raised by 25%, V(3)/V(4)(ATP)by 18% and ADP/O by 12% respectively.

摘要

我们研究了姜黄素对阿霉素诱导的氧化应激状态下心肌细胞活力、心肌细胞线粒体氧化磷酸化过程及其氧化还原平衡的影响。结果显示，给大鼠注射阿霉素后，线粒体中脂质过氧化的次级产物（硫代巴比妥酸反应物，TBARS）含量显著增加21%，过氧化氢（H₂O₂）含量显著增加76%；与对照组相比，线粒体锰超氧化物歧化酶（Mn-SOD）的酶活性降低了14%，而过氧化氢酶活性增强了80%。阿霉素与姜黄素联合使用后，TBARS和H₂O₂的含量分别增加了14%和26%，过氧化氢酶的酶活性降低了28%，线粒体Mn-SOD活性增强了9%。在与阿霉素共同孵育期间，活细胞数量相对于对照组减少了30.4%，坏死细胞数量增加了30.4%。阿霉素与姜黄素共同给药后，细胞活力增强了8%，而与仅使用阿霉素相比，坏死细胞数量减少了8%。在评估注射阿霉素的大鼠的线粒体呼吸参数时，主动呼吸指数（V₃）下降了43.8%，磷酸化偶联氧化率（V₃/V₄(ATP)）下降了47%，磷酸化效率指数（ADP/O）也分别下降了31.7%。与仅使用阿霉素相比，阿霉素与姜黄素联合使用改善了线粒体呼吸指标：V₃分别提高了25%，V₃/V₄(ATP)提高了18%，ADP/O提高了12%。