中国药理学与毒理学杂志2012，Vol.26Issue(5)：602-609,8.DOI:10.3867/j.issn.1000-3002.2012.05.002
左卡尼汀对过氧化氢诱导的心肌细胞凋亡的抑制作用
Inhibitory effect of L-carnitine on cardiomyocyte apoptosis induced by hydrogen peroxide
摘要
Abstract
OBJECTIVE To investigate the effect of L-carnitine on H2O2-induced apoptosis in cultured neonatal rat cardiomyocytes and its possible mechanisms.METHODS H2O2 200 μmol· L-1 was used to set up an oxidative stress induced injury model in neonatal rat cardiomyocytes.There were normal control,H2O2 200 μmol·L-1 model,L-carnitine (0.3,0.6 and 1.2 mmol· L-1 ),L-carnitine ( 1.2 mmol· L-1 ) + H2O2 ( 200 μmol· L-1 )groups in the experiment.The cells were pretreated with L-carnitine 0.3,0.6 and 1.2 mmol· L- 1 for 1 h before H2O2 200 μmol·L-1 was added for 12 h.Cell viability was measured by MTT assay and apoptosis was determined by flow cytometry.The expression of caspase 3 was determined by Western blotting.Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured according to the instructions of commercial kits. L-Carnitine 1.2 mmol· L- 1 was added 5 min prior to H2O2 200 μ mol· L- 1.H2O2 was perfused for 5 min to measure [Ca2 +] i transient by Till image system by cell loading Fura-2/AM.RESULTS Application of H2O2 200 μ mol ·L-1 to myocytes for 12 h could cause cardiomyocyte apoptosis.L-Carnitine 0.3,0.6 and 1.2 mmol· L-1 significantly reversed the lesion of primary cultured cardiomyocytes treated with H2O2 200 μmol· L-1,increased SOD activity (P ＜0.01 ),and decreased MDA content( P ＜0.01 ).L-Carnitine 1.2 mmol·L-1 was the most powerful in that it decreased caspase 3 expression(P ＜0.01 ) and the adverse effect of H2O2 on the [Ca2+]i transient was abolished by L-carnitine pretreatment.L-Carnitine had no effect on the elevation of the resting [Ca2+] i evoked by H2O2 in Ca2+ -free medium. CONCLUSION L-Carnitine can produce an inhibitory effect on cardiomyocyte apoptosis induced by H2O2,which may be mediated by the protective effect on the cell membrane and the damage to voltagedependent Ca2+ channel as well as its inhibition of lipid peroxidation.关键词
左卡尼汀/过氧化氢/肌细胞,心脏/细胞凋亡/细胞内钙离子Key words
L-carnitine/hydrogen peroxide/myocytes, cardiac/apoptosis/intracellular calcium分类
医药卫生引用本文复制引用
梁春光,戴红良,黄雷,王东海,王洪新..左卡尼汀对过氧化氢诱导的心肌细胞凋亡的抑制作用[J].中国药理学与毒理学杂志,2012,26(5):602-609,8.基金项目
The project supported by Program for Liaoning Excellent Talents in University (2008RC33) （2008RC33）
Liaoning Provincial Office of Education Innovation Project Team (2007T113) （2007T113）
辽宁省高等学校优秀人才支持计划项目(2008RC33) （2008RC33）
辽宁省教育厅优秀团队项目(2007T113) （2007T113）
