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活性氧和线粒体ATP敏感钾通道介导肿瘤坏死因子对缺氧/复氧心肌的保护作用

傅深, 曹春梅, 夏强, 杨俊, 陆源

浙江大学医学院生理学教研室，杭州310031

摘要

在培养的乳鼠心肌细胞上，研究肿瘤坏死因子。( TNF a)对缺氧/复氧损伤心肌的保护作用的机制。结果发现:(1)用TNF a (1。一500 U/ ml)预处理，缺氧/复氧后心肌细胞内锰超氧化物歧化酶( Mrr 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乙酞半肤氨酸(NA(，1 mmol/ L)、抗霉素A ( anti mycin A, 50 umol/L)、 2-琉基丙酞氨基乙酸(2- MPG, 400 umol/ L)和铜/锌超氧化物歧化酸(Ch/ Zn-SOD)抑制剂二乙基二硫代氨基甲酸盐mitoKATp通道开放剂diaeoxide (50 umol/ 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 umol/ L)和NA(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。对缺氧/复氧损伤的心肌保护作用。

关键词： 心肌细胞; 肿瘤坏死因子#alpha#TNF#alpha#; 缺氧; 复氧; 活性氧; 线粒体ATP敏感钾通道

Reactive oxygen species and mitochondrial KATP serritive channels mediated cardioprotection induced扮TNI- a during hypoxia and reoxygenation

FU Chen, CAO Chun Mei, XIA qang, Yang Jun, LU Yuan

Department of Physiology，Zhejiang University School of Medicine，Hangzhou

Abstract

The aim of the present study was to testify whether the reactive oxygen species and mitochondrial ATP- sensitive potassium(KATP) channels were involved in the cardioprotection induced妙tumor necrosis factor a (TNr- a) in the cultured neonatal ventricular myocytes suffered from 12 h of hypoxia and 6 h of reoxygenation.We tested the release of lactate dihydroge nase(LDH) and manganese superoxide dismutase(Ma-SOD) with spectrophotometay·It was shown that pretreatment with TNF=a(10，50，100，or 500 U/ ml) significantly in-
creased the Mar SOD activity and reduced LDH release in the neonatal ventricular myocytes subjected to hypoxia and reoxygenation·Pretreatment with NAC(1 mmol/ L)，antimycin A(50 p mol/ L)，2- MPG(400 pmol/L)，pectively，attenuated the increase in MLrSOD activity and reduction of LDH level induced by TNF=a in ventricular myocytes .Diazoxide(50 umol/L，a selective opener of
the mitochondrial KATP channel，decreased the LDH release of the myocytes su ected to hypoxia and reoxygenation，which could be abolished by pretreatment with NAC(1 mmol/ L) or 5- HD(100 p mol/ L).These results suggest that oxygen radical signals and mitochondrial KATP channels are involved in the cardioprotection induced by TNF#alpha#

Key words: myocytes;tumor necrosis factor a(TNr- a);hypoxia/ reoxygenation; reactive oxygen ;;

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引用本文：

傅深, 曹春梅, 夏强, 杨俊, 陆源. 活性氧和线粒体ATP敏感钾通道介导肿瘤坏死因子对缺氧/复氧心肌的保护作用[J]. 生理学报 2003; 55 (3): .

FU Chen, CAO Chun Mei, XIA qang, Yang Jun, LU Yuan. Reactive oxygen species and mitochondrial KATP serritive channels mediated cardioprotection induced扮TNI- a during hypoxia and reoxygenation. Acta Physiol Sin 2003; 55 (3): (in Chinese with English abstract).