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Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2020-03-12 , DOI: 10.1038/s41401-020-0382-x
Qiao-Qiao Cheng 1 , Yu-Wei Wan 1 , Wei-Min Yang 2 , Meng-Hua Tian 3 , Yu-Chuan Wang 3 , Hai-Yan He 3 , Wei-Dong Zhang 1 , Xuan Liu 1
Affiliation  

Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia–reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by H2O2. Pretreatment of GAS at 20, 50, and 100 μM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 μM H2O2 for 3 h. Furthermore, we showed that H2O2 treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; H2O2 treatment strongly inhibited mitochondrial respiration; H2O2 treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in H2O2-treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under H2O2 treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on H2O2-treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria.



中文翻译:


天麻素通过改善不平衡的线粒体动力学和线粒体功能障碍来保护 H9c2 心肌细胞免受氧化损伤



天麻素(GAS)是天麻的主要生物活性成分,天麻是一种广泛用于治疗神经系统疾病以及心脑血管疾病的中药。在本研究中,发现 GAS 对 H9c2 细胞免受缺血再灌注(IR)样损伤的保护作用与减少氧化应激有关。此外,GAS可以保护H9c2细胞免受H 2 O 2引起的氧化损伤。 20、50和100 μM GAS预处理4小时显着改善了用400 μM H 2 O 2处理3小时的H9c2细胞的细胞活力下降和细胞凋亡增加。此外,我们还发现,H 2 O 2处理可诱导线粒体断裂,并显着减少线粒体的网络、足迹和管状长度。 H 2 O 2处理强烈抑制线粒体呼吸; H 2 O 2处理诱导线粒体融合因子Mfn2和Opa1表达减少,线粒体裂变因子Fis1表达增加。 H 2 O 2处理的H9c2 细胞中的所有这些改变都可以通过GAS 预处理得到改善。此外,我们发现GAS预处理增强了H 2 O 2处理下Nrf2的核转位。 Nrf2 表达的敲低消除了 GAS 对 H 2 O 2处理的 H9c2 细胞的保护作用。 我们的结果表明,GAS 可能通过增加 Nrf2 的核转位、调节线粒体动力学、维持线粒体的结构和功能来保护 H9c2 心肌细胞免受氧化损伤。

更新日期:2020-04-24
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