PDF(Pubmed)
Abstract：
Oxidative stress is the main cause of ischemia/reperfusion injury. Propofol is a commonly used intravenous hypnotic anesthetic agent with antioxidant properties. In this study, we aimed to elucidate the protective effects of propofol on H2O2-induced cardiomyocyte injury and myocardial ischemic/reperfusion injury (MIRI) in rats. Cardiomyocyte injury was evaluated by determining cardiac troponin-1 (cTn-1) and creatine kinase-MB (CK-MB) levels. Antioxidative stress was assessed by measuring lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), reactive oxygen species (ROS), and catalase (CAT) levels. Apoptosis was evaluated using flow cytometry and TUNEL assays. Bax and Bcl-2 expression levels were determined by quantitative reverse transcription PCR (qRT-PCR) and Western blotting. The levels of glycogen synthase kinase 3 beta/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway-related factors were measured using Western blotting. Myocardial infarction in rats was analyzed using an Evans blue staining assay. The results showed that propofol reduced the levels of CK-MB, cTn-1, LDH, MDA, and ROS, and increased the levels of GSH, SOD, and CAT in H2O2-treated H9c2 cells. Additionally, propofol inhibited H2O2-induced apoptosis by downregulating Bax and upregulating Bcl-2. Moreover, propofol decreased the area of myocardial infarction in rats with MIRI. The GSK3β-Nrf2/HO-1 signaling pathway was activated by propofol. Rescue experiments showed that Nrf2 knockdown alleviated the effects of propofol on oxidative stress and apoptosis in H9c2 cells. In conclusion, propofol attenuated H2O2-induced myocardial cell injury by regulating the GSK3β/Nrf2/HO-1 signaling pathway and alleviating MIRI, suggesting that propofol is a promising therapeutic option for ischemic heart disease.
摘要：
氧化应激是招致缺血/再灌注毁伤的主要缘由。丙泊酚是一种常用的静脉催眠麻醉剂，具有抗氧化性能。在这项研究中,我们旨在阐明异丙酚对H2O2诱导的大鼠心肌细胞损伤和心肌缺血/再灌注损伤（MIRI）的保护作用。通过测定心肌肌钙蛋白-1(cTn-1)和肌酸激酶-MB(CK-MB)水平评价心肌细胞损伤。通过测量乳酸脱氢酶（LDH）评估抗氧化应激，丙二醛（MDA），谷胱甘肽(GSH),超氧化物歧化酶（SOD），活性氧（ROS），和过氧化氢酶(CAT)水平。使用流式细胞术和TUNEL测定评估细胞凋亡。通过定量逆转录PCR(qRT-PCR)和Western印迹测定Bax和Bcl-2表达水平。采用Westernblotting检测糖原合成酶激酶3β/核因子红系2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)通路相关因子水平。使用Evans蓝染色测定法分析大鼠的心肌梗塞。结果表明，异丙酚降低了CK-MB的水平，cTn-1,LDH,MDA,ROS,并增加了GSH的水平，SOD,和CAT在H2O2处理的H9c2细胞中。此外,异丙酚通过下调Bax和上调Bcl-2抑制H2O2诱导的细胞凋亡。此外，异丙酚减少了MIRI大鼠的心肌梗死面积。丙泊酚激活GSK3β-Nrf2/HO-1信号通路。抢救实验表明，Nrf2敲除减轻异丙酚对H9c2细胞氧化应激和凋亡的影响。总之,异丙酚通过调节GSK3β/Nrf2/HO-1信号通路减轻MIRI,减轻H2O2诱导的心肌细胞损伤,提示异丙酚是缺血性心脏病的一种有前景的治疗选择.
