Paeoniflorin protects myocardial cell from doxorubicin-induced apoptosis through inhibition of NADPH oxidase
Paeoniflorin protects myocardial cell from doxorubicin-induced apoptosis through inhibition of NADPH oxidase
复制标题
Paeoniflorin 通过抑制 NADPH 氧化酶来保护心肌细胞免受阿霉素诱导的细胞凋亡。
DOI：
10.1139/y2012-140
复制
发表时间：
2012-12-01
影响因子：
2.1
通讯作者：
Dong, Xiao-Min
中科院分区：
文献类型：
--
作者：
Li, Jian-Zhe;Yu, Shu-Yi;Dong, Xiao-Min
多柔比星(DOX)诱导的心肌细胞凋亡与细胞内活性氧(ROS)增加有关，而芍药苷(PEF)具有抗氧化作用。本研究旨在探讨PEF对DOX诱导的心肌细胞凋亡的保护作用及其机制。在培养的H9c2细胞中，加入不同浓度(1、10、100μ摩尔/L)的PEF作用2 h后，再加入DOX(5μ摩尔/L)作用24 h，Hoechst 33342染色检测细胞凋亡率，半胱氨酸天冬氨酸氨基转移酶-3表达及活性变化。用实时定量聚合酶链式反应和Western印迹法分别检测NADPH氧化酶(NOX)2和NOX4的mRNA和蛋白表达。用试剂盒检测细胞内ROS和NOX活性。结果表明，DOX可显著增加心肌细胞的凋亡率，增加caspase-3的表达和活性，同时增加ROS的产生，增加NOX2、NOX4的mRNA和蛋白表达以及NOX的活性。PEF可显著抑制上述作用。我们的结果提示，PEF通过抑制NOX2、NOX4的表达和NOX的活性来减少ROS的产生，从而对DOX诱导的心肌细胞凋亡具有保护作用。
Increased intracellular reactive oxygen species (ROS) are involved in doxorubicin (DOX)-induced myocardial cell apoptosis, and paeoniflorin (PEF) has been shown to exert an antioxidant effect. The aim of the present study was to explore the protective effect of PEF on DOX-induced myocardial cell apoptosis and the underlying mechanisms. In cultured H9c2 cells, different concentrations (1, 10, or 100 μmol/L) of PEF was added for 2 h prior to exposure to DOX (5 μmol/L) for 24 h. Cell apoptosis was evaluated by hoechst 33342 staining, and caspase-3 expression and activity. The mRNA and protein expression of NADPH oxidase (NOX) 2 and NOX4 was determined by real-time polymerase chain reaction and Western blot, respectively. Intracellular ROS and NOX activity were measured by assay kit. The results showed that DOX significantly increased myocardial cell apoptosis, increased caspase-3 expression and activity concomitantly with enhanced ROS production, and increased NOX2, NOX4 mRNA and protein expression, and NOX activity. These effects were remarkably inhibited by pretreatment of PEF. Our results suggested that PEF has a protective effect against DOX-induced myocardial cell apoptosis through a mechanism involving a decrease in ROS production by inhibition of NOX2, NOX4 expression, and NOX activity.