激动维甲类X受体抑制过氧化氢诱导的心肌细胞凋亡

The effect of activating retinoid X receptor inhibiting hydrogen peroxide-induced apoptosis in cultured rat neonatal cardiornyoeytes

目的探讨维甲类X受体（retinoid X receptor，RXR）激动剂9-顺式维甲酸（9-cis retinoid acid，c-RA）对过氧化氢（hydrogen peroxide，H2O2）诱导的体外培养大鼠心肌细胞凋亡的影响及其机制。方法以培养的新生Sprague-Oawley（SD）大鼠心肌细胞为实验对象，随机分为三组：正常对照组（N组）、100μmol／L H2O2刺激组（H组）和100nmol／L c-RA干预组（H＋R组）。应用MTF法检测细胞活力，以Hoechst 33258荧光染色观察凋亡细胞，流式法检测细胞凋亡比率，JC-1荧光染色法检测细胞线粒体膜电位（△Ψm）变化，CM-H2DCFDA荧光探针测定细胞内活性氧（reactive oxygen species，ROS）水平。所有计量资料以均数±标准差（-↑x±s）表示，采用单因素方差分析，Dunnett-t检验，以P〈0．05为差异具有统计学意义。结果c-RA明显增强H2O2刺激后的心肌细胞活力，减少凋亡比例，稳定线粒体膜电位，减轻细胞活性氧产生。结论RXR受体激动剂c-RA能够部分抑制H2O2诱导的心肌细胞凋亡，其机制可能与减轻细胞氧化应激损伤有关。

Objective To investigate the effect of 9-cis retinoid acid （c-RA）, a retinoid X receptor （RXR） agonist, on hydrogen peroxide （H2O2） induced apoptosis in cultured rat neonatal cardiomyocytes, and to explore the mechanism. Method Cultured cardiomyocytes were randomly divided into three groups：normal group treated with vehicle （N group）, H2O2 group treated with 100 μmol/L H2O2（H group） ,and c-RA group pretreated with 100nmol/L c-RA （ H ＋ R group）. Cell viability was detected by MTT. Morphological changes of apoptotic cardiomyocytes were observed by Hoechst 33258 staining under fluorescence microscope. The apoptotic rate was determined by flow cytometry. Mitochondrial membrane potential（△Ψm）was measured by JC-1 dye. Cellular reactive oxygen species（ ROS）production was detected by CM-H2DCFDA fluorescent probe. All measurement data wre expressed as （ -↑x ± s ）, and statistically analyzed using one-way ANOVA analysis and Dunnett test. Differences were considered significant when P was 〈 0.05. Results Treatment with c-RA significantly enhanced cell viability,reduced apoptosis ratio, stabled mitochondrial membrane potential and reduced level of cellular reactive oxygen species. Conclusions RXR agonist c-RA inhibits H2O2-induced myocyte apoptosis in cultured rat neonatal cardiomyocytes, which may be related to alleviate oxidative stress injury.