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Reactive oxygen species and mitochondrial KATP-sensitive channels mediated cardioprotection induced by TNF-α during hypoxia and reoxygenation
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- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 3
- DOI:
- 10.3321/j.issn:0371-0874.2003.03.009
- Key Word:
- 心肌细胞;肿瘤坏死因子α (TNF-α);缺氧;复氧;活性氧;线粒体ATP敏感钾通道
Abstract： 在培养的乳鼠心肌细胞上, 研究肿瘤坏死因子α (TNF-α)对缺氧/复氧损伤心肌的保护作用的机制.结果发现: (1) 用TNF-α (10-500 U/ml)预处理, 缺氧/复氧后心肌细胞内锰超氧化物歧化酶(Mn-SOD)活性增高、乳酸脱氢酶(LDH)释放量减少(P<0.05); (2) 用抗氧化剂N-乙酰半胱氨酸 (NAC, 1 mmol/L)、抗霉素A (antimycin A, 50 μmol/L)、2-巯基丙酰氨基乙酸(2-MPG, 400 μmol/L)和铜/锌超氧化物歧化酸(Cu/Zn-SOD)抑制剂二乙基二硫代氨基甲酸盐(DDC, 100 nmol/L)预处理, 可取消TNF-α的抑制缺氧/复氧心肌细胞LDH释放和诱导Mn-SOD活性增高的作用; (3) mitoKATP通道抑制剂5-羟基GB9EF酸(5-HD)预处理可阻断TNF-α对缺氧/复氧心肌细胞的保护作用; 选择性mitoKATP通道开放剂diazoxide (50 μmol/L)预处理可减少复氧后心肌细胞LDH的释放(P<0.01), 其作用可被5-HD (100 μmol/L)和NAC所抑制.上述结果表明, 活性氧和线粒体ATP敏感钾通道参与介导TNF-α对缺氧/复氧损伤的心肌保护作用.
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