活性氧、NO和线粒体ATP敏感钾通道在TNF-α预处理对缺血/再灌注心肌保护中的作用

ROLE OF REACTIVE OXYGEN SPECIES,NITRIC OXIDE AND MITOCHONDRIAL K ATP CHANNELS IN TNF-ALPHA INDUCED CARDIOPROTECTION

目的 :观察TNF α预处理对缺血 /再灌注心脏功能和酶学指标的影响及其可能机制。方法 :采用心脏Lan gendorff灌流模型。 结果 :与单独缺血 /再灌注组相比 ,TNF α(10 4U/L)预处理明显减弱缺血 /再灌注对左室发展压、左室舒张末压、最大收缩 /舒张速率和左室发展压与心率乘积的抑制作用 (P <0 .0 5 ) ,并显著降低复灌后冠脉流出液中乳酸脱氢酶 (LDH)含量 ,增加线粒体中锰超氧化物歧化酶 (Mn SOD)活性 (P <0 .0 5 ) ;分别使用抗氧化剂 2 MPG(0 .3mmol/L)、一氧化氮合酶抑制剂L NAME(0 .5mmol/L)或线粒体ATP敏感钾通道抑制剂 5 HD(10 0μmol/L)预处理 ,减弱了TNF α改善缺血 /再灌注后心功能、抑制心肌LDH释放和诱导Mn SOD活性增高的作用。结论 :TNF α预处理具有减轻心脏缺血 /再灌注损伤的作用 ,这一作用可能与其诱导Mn SOD活性增高有关 ,活性氧、一氧化氮和线粒体ATP敏感钾通道参与介导TNF α的心肌保护作用。

Aim: To explore the cardiac effect of TNF-α in postischemic heart and the possible mechanism. Methods: Langendorff perfused rat heart was used to evaluate the contractile properties of myocardium by intraventricular pressure measurement.The isolated rat heart underwent 20 min of global ischemia followed by 20 min of reperfusion.The level of lactate dehydrogenase(LDH) in the coronary effluent was measured to evaluate the cardiac injury.And the activity of manganese superoxide dismutase(Mn-SOD)in myocardium was measured. Results: Perfusion with TNF-α (10 4U/L) attenuated the inhibitory effects induced by ischemia/reperfusion on left ventricular developed pressure(LVDP),left ventricular end-diastolic pressure(LVEDP),maximal rise/fall rate of left ventricular pressure(±dP/dt max ) and rate pressure product(LVDP multiplied by heart rate,LVDP×HR).TNF-α significantly decreased the release of LDH(P<0.05) and increased the activity of Mn-SOD in the myocardium(P<0.05).Antioxidant 2-MPG(0.3 mmol/L),NOS inhibitor L-NAME(0.5 mmol/L)or mitochondrial selective K ATP channel inhibitor 5-HD(100 μmol/L)attenuated the increase in LVDP,±dP/dt max and LVDP×HR,and decrease in LVEDP induced by TNF-α in ischemia/reperfusion heart,respectively.And the effects of TNF-α in reducing the levels of LDH and increasing the Mn-SOD activity were also attenuated by 2-MPG,L-NAME or 5-HD,respectively. Conclusion: TNF-α pretreatment attenuates the myocardial injury induced by ischemia/reperfusion,which coincides with the increasing of myocardial Mn-SOD activity.Reactive oxygen species,nitric oxide and mitochondrial K ATP channels are involved in the cardioprotection induced by TNF-α.