氟烷、七氟醚肝毒性与肝细胞钙平衡

The relation between the hepatotoxicity of halothane and sevoflurane and altered hepatic calcium homeostasis

目的:研究卤代类吸入麻醉药肝毒性与肝细胞钙平衡的关系。方法：应用酶诱导缺氧大鼠模型、Ca(2＋)细胞化学定位法、EDX电镜微量元素分析、离体大鼠肝细胞及肝脏微粒体Ca(2＋)摄取及释放、肝脏显微病理的体视学分析及肝脏超微病理的电子计算机图像处理等技术，从生化及形态学角度探讨肝脏细胞钙平衡的改变在氟烷性肝炎发生发展中的重要作用，并与七氟醚进行对比研究，观察其与氟烷的异同。结果：在酶诱导缺氧条件下，吸入氟烷可造成明显的肝损害，而同样情况下吸入七氟醚则无明显肝损害。氟烷可致肝细胞胞浆及线粒体钙负荷增加。结论：提示肝细胞Ca(2＋)平衡的改变在氟烷性肝炎的发生发展中起着重要作用。七氟醚对肝细胞钙平衡影响较小．亦无明显肝毒性。

To investigate the relation between the hepatotoxicity of halothane and sevofluraneand altered hepatic calcium homeostasis. Methods: Enzyme-induced, hypoxic rat model and isolated modelwere used in this study. The necrosis and denaturation of liver were quantltatlvely estimated by stereoscopy. Ultrastructural morphology was analysed by computer. Calcium was select1vely localized with oxalate- pyroantimomate precipitation procedured and determlned by EDX microanalysis. lsolated rat hepato-cytes and hepatic microsomes were incubated in 45Ca2+ media containing 1. 25 μl/ml halothane or sevoflu-rane. The effects of halothane and sevoflurane on hepatocytes and hepatic microsomes uptake and releaseof 45Ca2+ were investigated. Results: The liver of all rats given halothane (14 %O2 ) had extensive centrilob-ular necrosis and denaturation. A large amount of calcium deposition was shown in cytoplasm and mito-chondria in hypoxic halothane group. Halothane and sevoflurane accelerated the uptake of 45Ca2+ by thehepatocytes. The release of the loaded 45Ca2+ by halothane decreased significantly. There was n0 effect ofsevoflurane on release 0f the loaded 'Ca2+. Microsomal 45Ca2+ uptake was released 24 h after halothane ex-posure as compared with control and sevoflurane exposure. Conclusion: Increased cyt0solic Ca2+ concen-tration is implicated in the mechanism of halothane-induced hepatotoxicity. Sevoflurane has fewer effectson hepatic calcium homeostasis than halothane.