低氧环境下丙泊酚可增加PC12细胞的凋亡
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摘要
目的探讨低氧环境下丙泊酚对PC12细胞株凋亡的影响及机制。方法将PC12细胞接种于培养板中,采用随机数字表法,将其随机分为6组:低氧对照组(CH组)、空气对照组(CA组)和氧气对照组(CO组),对照组加入脂肪乳浓度10μmol/L。丙泊酚低氧组(PH组)、丙泊酚空气组(PA组)和丙泊酚氧气组(PO组),丙泊酚浓度为10μmol/L。药物处理完毕后分别放入低氧(5%O_2),空气和氧气(35%O_2)环境的细胞培养箱培养,8 h后流式检测细胞凋亡情况,检测细胞内ROS水平和细胞SOD酶活力。结果与CA组比较,PA组细胞凋亡增加,活性氧簇(ROS)升高,超氧化物歧化酶(SOD)活力增强;与CH组比较,PH组细胞凋亡增加,ROS升高,SOD活力增强;与CO组比较,PO组细胞凋亡增加,ROS升高,SOD活力增强;与PA组比较,PH细胞凋亡增加,ROS升高,SOD活力增强;CO组、CA组和CH组上述各指标差异无统计学意义。结论低氧环境下丙泊酚可通过氧化应激损伤导致PC12细胞凋亡增加。
Objective To investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions. Methods PC12 cells were exposed to room air, 35% oxygen, or 5% oxygen(hypoxia) for 24 h in the presence of either 10 μmol/L lipid emulsion or 10 μmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species(ROS) and the activity of superoxide dismutase(SOD) were evaluated.Results In room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen. Conclusion Under hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.
Objective To investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions. Methods PC12 cells were exposed to room air, 35% oxygen, or 5% oxygen(hypoxia) for 24 h in the presence of either 10 μmol/L lipid emulsion or 10 μmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species(ROS) and the activity of superoxide dismutase(SOD) were evaluated.Results In room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen. Conclusion Under hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.
引文
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[14]Kahraman S,Demiryurek AT.Propofol is a peroxynitrite scavenger[J].Anesth Analg,1997,84(5):1127-9.
[15]Li YJ,Zhong DD,Lei L,et al.Propofol prevents renal Ischemiareperfusion injury via inhibiting the oxidative stress pathways[J].Cell Physiol Biochem,2015,37(1):14-26.
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[17]Bellanti F,Mirabella L,Mitarotonda D,et al.Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1 activation in hepatic ischemia/reperfusion injury[J].Free Radical Biol Med,2016,96:323-33.
[18]Xu ZJ,Yu J,Wu JB,et al.The effects of two anesthetics,propofol and sevoflurane,on liver ischemia/reperfusion injury[J].Cell Physiol Biochem,2016,38(4):1631-42.
[19]Wang JW,Cheng WW,Xu T,et al.Propofol induces apoptosis and inhibits the proliferation of rat embryonic neural stem cells via gamma-aminobutyric acid type A receptor[J].Genet Mol Res,2015,14(4):14920-8.
[20]Sun WC,Liang ZD,Pei L.Propofol-induced rno-mi R-665 targets BCL2L1 and influences apoptosis in rodent developing hippocampal astrocytes[J].Neurotoxicology,2015,51:87-95.
[21]Wang XB,Cheng YH,Liu XJ,et al.Unexpected pro-injury effect of propofol on vascular smooth muscle cells with increased oxidative stress[J].Crit Care Med,2011,39(4):738-45.
[22]于布为,薛庆生,夏梦,等.丙泊酚对大鼠脑片不同性质损伤的影响[J].中华医学杂志,2003,83(13):1176-9.
[2]Konno A,Nishimura A,Nakamura S,et al.Continuous monitoring of caspase-3 activation induced by propofol in developing mouse brain[J].Int J Dev Neurosci,2016,51:42-9.
[3]Han D,Jin JH,Fang H,et al.Long-term action of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rats[J].Int J Clin Exp Med,2015,8(7):10696-704.
[4]Chen C,Xu GH,Li YH,et al.Selective impairment of attention networks during propofol anesthesia after gynecological surgery in middle-aged women[J].J Neurol Sci,2016,363:126-31.
[5]Zhang B,Dong YL,Zhang GH,et al.The inhalation anesthetic desflurane induces caspase activation and increases amyloid betaprotein levels under hypoxic conditions[J].J Biol Chem,2008,283(18):11866-75.
[6]Concas A,Santoro G,Mascia MP,et al.The general anesthetic propofol enhances the function of gamma-aminobutyric acidcoupled chloridechannel in the rat cerebral cortex[J].J Neurochem,1990,55(6):2135-8.
[7]Chikutei KI,Oyama TM,Ishida S,et al.Propofol,an anesthetic possessing neuroprotective action against oxidative stress,promotes the process of cell death induced by H2O2in rat thymocytes[J].Eur J Pharmacol,2006,540(1/3):18-23.
[8]Konishi T.Brain oxidative stress as basic target of antioxidant tradi.tional oriental medicines[J].Neurochem Res,2009,34(4):711-6.
[9]Kizaki M,Xian M,Sagawa M,et al.Induction of apoptosis via the modulation of reactive oxygen species(ROS)production in the treatment of myeloid leukemia[J].Curr Pharm Biotechnol,2006,7(5):323-9.
[10]Otitoju O,Onwurah IE,Otitoju GO,et al.Oxidative stress and superoxide dismutase activity in brain of rats fed with diet containing permethrin[J].Biokemistri,2008,20(2):93-8.
[11]Sada K,Nishikawa T,Kukidome DA,et al.Hyperglycemia induces cellular hypoxia through production of mitochondrial ROS followed by suppression of aquaporin-1[J].PLo S One,2016,11(7):e0158619.
[12]Pearn ML,Hu Y,Niesman IR,et al.Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation[J].Anesthesiology,2012,116(2):352-61.
[13]Kolamunne RT,Dias IH,Vernallis AB,et al.Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts;the roles of reactive oxygen and nitrogen species[J].Redox Biol,2013,1(1):418-26.
[14]Kahraman S,Demiryurek AT.Propofol is a peroxynitrite scavenger[J].Anesth Analg,1997,84(5):1127-9.
[15]Li YJ,Zhong DD,Lei L,et al.Propofol prevents renal Ischemiareperfusion injury via inhibiting the oxidative stress pathways[J].Cell Physiol Biochem,2015,37(1):14-26.
[16]Green TR,Bennett SR,Nelson VM.Specificity and properties of propofol as an antioxidant free radical scavenger[J].Toxicol Appl Pharmacol,1994,129(1):163-9.
[17]Bellanti F,Mirabella L,Mitarotonda D,et al.Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1 activation in hepatic ischemia/reperfusion injury[J].Free Radical Biol Med,2016,96:323-33.
[18]Xu ZJ,Yu J,Wu JB,et al.The effects of two anesthetics,propofol and sevoflurane,on liver ischemia/reperfusion injury[J].Cell Physiol Biochem,2016,38(4):1631-42.
[19]Wang JW,Cheng WW,Xu T,et al.Propofol induces apoptosis and inhibits the proliferation of rat embryonic neural stem cells via gamma-aminobutyric acid type A receptor[J].Genet Mol Res,2015,14(4):14920-8.
[20]Sun WC,Liang ZD,Pei L.Propofol-induced rno-mi R-665 targets BCL2L1 and influences apoptosis in rodent developing hippocampal astrocytes[J].Neurotoxicology,2015,51:87-95.
[21]Wang XB,Cheng YH,Liu XJ,et al.Unexpected pro-injury effect of propofol on vascular smooth muscle cells with increased oxidative stress[J].Crit Care Med,2011,39(4):738-45.
[22]于布为,薛庆生,夏梦,等.丙泊酚对大鼠脑片不同性质损伤的影响[J].中华医学杂志,2003,83(13):1176-9.