线粒体渗透转换孔在肿瘤坏死因子α诱导的抗心肌缺氧/复氧损伤中的作用

目的：研究肿瘤坏死因子α（TNFα）诱导的抗心肌缺氧/复氧损伤的保护作用是否与抑制线粒体渗透转换孔的开放有关。 方法： 采用离体大鼠心脏灌流方法，结扎冠状动脉左前降支30 min和复氧120 min复制局部缺氧/复氧损伤模型，测定心肌梗死面积、冠脉流出液中乳酸脱氢酶（LDH）含量及各项心室力学指标。 结果： 与单纯缺氧/复氧组相比，1×104 U/L TNFα预处理明显降低心脏缺氧/复氧后的梗死面积和复氧期冠脉流出液中LDH含量，促进左室发展压、左室做功和左室舒张末压力的恢复。线粒体渗透转换孔开放剂atractyloside和钙激活钾通道阻断剂paxilline减弱了TNFα的作用。 结论： TNFα诱导的抗心肌缺氧/复氧损伤的保护作用可能与其抑制线粒体渗透转换孔的开放及促进钙激活钾通道的开放有关。

Role of mitochondrial permeability transition pore in TNFα- induced cardioprotection in isolated rat hearts subjected to hypoxia and reoxygenation

AIM: To investigate whether tumor necrosis factor α (TNFα) pretreatment can inhibit mitochondrial permeability transition pore opening in isolated rat hearts subjected to hypoxia and reoxygenation. METHODS: Isolated perfused rat hearts were subjected to 30 min regional hypoxia (occlusion of left anterior descending artery) and 120 min reoxygenation. The infarct size, lactate dehydrogenase (LDH) release during reoxygenation and ventricular hemodynamic parameters were measured. RESULTS: Pretreatment with TNFα at concentration of 1×104 U/L for 7 min followed by 10 min washout reduced the infarct size and LDH release, and improved the left ventricular performance (left ventricular developed pressure and rate-pressure product) and left ventricular end-diastolic pressure during hypoxia and reoxygenation. Administration of atractyloside (Atr, an opener of mitochondrial permeability transition pore, 20 μmol/L) for 20 min (last 5 min of hypoxia and first 15 min of reoxygenation) and paxilline (Pax, a calcium activated potassium channel antagonist, 1 μmol/L) for 5 min before hypoxia attenuated the reduction of infarct size and LDH release and improved the left ventricular performance induced by TNFα. CONCLUSION: The findings indicate that in the isolated rat heart model, TNFα protects myocardium against hypoxia and reoxygenation injury via inhibiting mitochondrial permeability transition pore opening as well as activating calcium, activated potassium channel.