Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes
Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes
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DOI：
10.1007/s10495-017-1349-3
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发表时间：
2017-05-01
期刊：
影响因子：
7.2
通讯作者：
Tan, Xiao-Qiu
中科院分区：
文献类型：
--
作者：
Liu, Xue-Ru;Cao, Lu;Tan, Xiao-Qiu
以往的研究表明，丙泊酚，一种临床常用的静脉麻醉剂，保护心肌免受损伤。线粒体和内质网（ER）介导的氧化应激和细胞凋亡是参与心肌损伤和保护的两条重要信号通路。本研究旨在验证丙泊酚通过上述两种途径发挥心脏保护作用的假设。培养的乳鼠心肌细胞分别用培养基（对照组）、500 μ M H2 O2（H2 O2组）、50 μ M丙泊酚（丙泊酚组）和H2 O2+丙泊酚（H2 O2+丙泊酚组）处理。采用酶联免疫吸附试验（ELISA）、流式细胞术、免疫荧光显微镜和Western blotting等方法检测心肌细胞的氧化应激、线粒体膜电位（DeltaIm）和凋亡。异丙酚可显著抑制H2 O2诱导的caspase 3、8、9和12活性、Bax/Bcl-2比值和细胞凋亡。异丙酚还抑制H2 O2诱导的活性氧（ROS）产生、乳酸脱氢酶（LDH）释放和线粒体跨膜电位（Delta Im）去极化，并恢复H2 O2诱导的谷胱甘肽（GSH）和超氧化物歧化酶（SOD）的还原。此外，丙泊酚降低了葡萄糖调节蛋白78 kDa（Grp 78）和肌醇需要酶1 α（IRE 1 α）的表达，这两种分子是ER介导的凋亡途径中的两种重要信号分子。异丙酚通过抑制线粒体和内质网介导的凋亡信号通路保护H2 O2诱导的心肌细胞损伤。
Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500 mu M (H2O2 group), propofol at 50 mu M (propofol group), and H2O2 plus propofol (H2O2 + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (Delta Im) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H2O2-induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H2O2-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (Delta Im) depolarization, and restored the H2O2-induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1 alpha (IRE1 alpha), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H2O2-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.