Liu Xue-Ru, Cao Lu, Li Tao, Chen Lin-Lin, Yu Yi-Yan, Huang Wen-Jun, Liu Li, Tan Xiao-Qiu
Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Key Laboratory of Medical Electrophysiology, Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China.
Apoptosis. 2017 May;22(5):639-646. doi: 10.1007/s10495-017-1349-3.
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), HO at 500 μM (HO group), propofol at 50 μM (propofol group), and HO plus propofol (HO + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) 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 HO-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 HO-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the HO-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 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from HO-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.
以往研究表明，丙泊酚作为临床常用的静脉麻醉药，可保护心肌免受损伤。线粒体和内质网（ER）介导的氧化应激和凋亡是参与心肌损伤与保护的两条重要信号通路。本研究旨在验证丙泊酚可通过上述两条通路发挥心脏保护作用这一假说。分别用培养基（对照组）、500 μM的HO（HO组）、50 μM的丙泊酚（丙泊酚组）以及HO加丙泊酚（HO＋丙泊酚组）处理培养的新生大鼠心肌细胞。通过包括ELISA、流式细胞术、免疫荧光显微镜检查和蛋白质印迹法在内的一系列检测方法评估心肌细胞的氧化应激、线粒体膜电位（ΔΨm）和凋亡情况。丙泊酚显著抑制HO诱导的半胱天冬酶3、8、9和12活性升高、Bax/Bcl-2比值升高以及细胞凋亡。丙泊酚还抑制HO诱导的活性氧（ROS）生成、乳酸脱氢酶（LDH）释放和线粒体跨膜电位（ΔΨm）去极化，并恢复HO诱导的谷胱甘肽（GSH）和超氧化物歧化酶（SOD）降低。此外，丙泊酚降低了葡萄糖调节蛋白78 kDa（Grp78）和肌醇需求酶1α（IRE1α）的表达，这两种蛋白是内质网介导的凋亡通路中的重要信号分子。丙泊酚通过抑制线粒体和内质网介导的凋亡信号通路保护心肌细胞免受HO诱导的损伤。
