吸入麻醉药对离体鼠肝线粒体跨膜电位的影响

Effect of volatile anesthetics on mitochondrial membrane potential in isolated rat liver mitochondria

目的 :通过观察吸入麻醉药对离体鼠肝线粒体跨膜电位的影响 ,研究吸入麻醉药肝毒性与线粒体能量代谢的关系。方法 :应用碱性藏红为探针 ,在 3ml的反应体系中分别加入 5、10、2 0、5 0μl/ ml氟烷、恩氟烷、异氟烷及七氟烷 ,用 UV - 30 0 0分光光度计进行双波长 (5 11～ 5 33nm )扫描 ,观察上述 4种药物对 ATP或琥珀酸能化及非能化鼠肝线粒体跨膜电位 (Δψ)的影响。结果 :氟烷与经典的解耦联剂氰化 -对 -三氟甲氧基苯腙相似 ,能明显降低能化及非能化线粒体的跨膜电位 ,而其余 3种药物仅在大剂量时才降低线粒体的跨膜电位。结论 :氟烷具有解耦联作用。氟烷与其他吸入麻醉药在能量代谢上的这种差异是否为它们肝毒性差异的原因值得引起重视。

Objective:To investigate the relationship between the hepatotoxicity of volatile anesthetics and mitochondrial energy metabolism by observing the effects of volatile anesthetics on mitochondrial membrane potential in isolated rat liver mitochondria.Methods:Samples of mitochondrial suspension (1.2 mg protein/ml) were exposed to 5,10,20,50 μl halothane,enflurane,isoflurane,sevoflurane, respectively. Membrane potential (Δψ) was monitored in the presence of 10 μmol/L safranine with scanning dual wavelength spectrophotometer at the wavelenth pair(511 533 nm). Results:Halothane was similar to an uncoupler of oxidative phosphorylation (FCCP) which reduced membrane potential, it was identical to that observed upon energization of the mitochondria by succinate or ATP. In contrast, enflurane, isoflurane and sevoflurane had less disturbances on liver mitochondrial membrane potential. Conclusion:Halothane is an inhibitor of oxidative phosphorylation, it is also an uncoupling agent at very high concentrations.These mitochondrial abnormalities is implicated in the mechanism of hepatotoxicity.