吸入麻醉药对离体鼠肝线粒体呼吸功能的影响

Effects of volatile anesthetics on rat liver mitochondrial respiration

应用离体鼠肝线粒体在体外研究了七氟醚、安氟醚、异氟醚、氟烷对其呼吸功能的影响。这四种吸入麻醉药在高剂量(>80μl/2.5ml)时均可对以琥珀酸为底物的ADP刺激的Ⅲ态线粒体呼吸有明显的抑制作用。氟烷的抑制作用最为明显,而且在高于临床剂量时,氟烷明显降低磷氧比(P/O)和氧化磷酸化效率(OPR),其它三种药物无类似作用。结果提示这四种药物均可抑制线粒体的呼吸功能、均具有潜在的肝毒性,并以氟烷为甚。

Isolated rat liver mitochondria model was used in this study to investigate the effects of halothane, sevoflurane, isoflurane and enflurane on oxidative phosphorylation of liver mitochondria. Mitochondria were prepared from liver obtained from male Spague-Dawley rats. The liver mitochondria were isolated in 70 mM sucrose, 220mM mannital, 2mM Hepes. 0.5 mM bovine serum albumin(pH7.4). Liver mitochondrial concentration was adiusted with buffer to obtain a final concentration of 30-40mg protein per ml. Liver mitochondria was randomly divided into 13 groups with equal number of 7 in each group and were exposed to low. middle, high concentration of halothane. enflurane, isoflurane and sevoflurane. The actions of volatile anesthetics on rat liver mitochondrial respiration were studied in vitro by oxygen electrode. These anesthetics markedly inhihited ADP-stimulated-respiration (state 3) of liver mitoehondria at very high concentrations with succinate as substrate. The sensitivity to inhibition by halothane was greater than the other anesthetics. At higher than clinical concentration, halotbane significantly depressed P/O and oxidative p sphorylation rate. This effect was not seen with mitochondria respiration in the presence of sevoflurane. enflurane and isoflurane. These results suggest that halothane is an inhibitor of oxidative phosphorylation and also an uncoupling agent at very high coneenteations.