Cheng Yongxia, Feng Yukuan, Zhu Min, Yan Bin, Fu Songbin, Guo Jin, Hu Jing, Song Xiandong, Guo Sufen, Liu Guibo
Department of Pathology, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China; Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang Province 150086, People's Republic of China.
Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang Province 150086, People's Republic of China; Department of Anatomy, Mudanjiang Medical College, Mudanjiang, Heilongjiang Province 157011, People's Republic of China.
Acta Histochem. 2014 Jan;116(1):214-21. doi: 10.1016/j.acthis.2013.07.007. Epub 2013 Jul 31.
The aim of the present study was to investigate the protective effects of T0901317 (T0), a potent agonist of liver X receptors (LXRs), on high glucose-induced oxidative stress and apoptosis in H9c2 cardiac cells. Exposure of H9c2 cells to high glucose alone, not only caused a significant increase in apoptosis and reactive oxygen species (ROS) generation, but also led to a decrease in mitochondrial membrane potential (ΔΨm), release of cytochrome c, decrease in Bcl-2, increase in Bax expression and the activation of caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-κB. However, pretreatment with T0 effectively decreased apoptosis, reduced the levels of ROS, abrogated ΔΨm, inhibited cytochrome c release and NF-κB activation, increased Bcl-2 and decreased Bax expression. In conclusion, our data suggest that T0 exerts protective effects against high glucose-induced apoptosis in H9C2 cardiac muscle cells via inhibition of ROS production, mitochondrial death and NF-κB activation.
本研究的目的是探讨肝脏X受体（LXRs）的强效激动剂T0901317（T0）对高糖诱导的H9c2心肌细胞氧化应激和凋亡的保护作用。单独将H9c2细胞暴露于高糖环境中，不仅会导致凋亡和活性氧（ROS）生成显著增加，还会导致线粒体膜电位（ΔΨm）降低、细胞色素c释放、Bcl-2减少、Bax表达增加以及半胱天冬酶-3、半胱天冬酶-9、聚（ADP-核糖）聚合酶（PARP）和核因子（NF）-κB激活。然而，用T0预处理可有效减少凋亡、降低ROS水平、消除ΔΨm、抑制细胞色素c释放和NF-κB激活、增加Bcl-2并降低Bax表达。总之，我们的数据表明，T0通过抑制ROS产生、线粒体死亡和NF-κB激活，对高糖诱导的H9C2心肌细胞凋亡发挥保护作用。
