异氟烷对离体大鼠心脏缺血后能量代谢的影响及其机制  

Effect and Mechanisms of Isoflurane on energy metabolism after Ischemia in Isolated Rat Hearts [WT5BZ]

作　　者：许鹏程[1] 许诺[2] 王义桥 范建伟[1] 

机构地区：[1]徐州医学院麻醉药理学教研室.江苏省麻醉学重点实验室,江苏徐州221002 [2]徐州医学院临床医学系,江苏徐州221002

出　　处：《中国药理学通报》2006年第12期1494-1499,共6页Chinese Pharmacological Bulletin

基　　金：江苏省卫生厅科研基金资助项目(NoH9908)

摘　　要：目的研究异氟烷对心肌缺血/再灌注期间能量代谢和功能的影响及其可能机制。方法实验采用离体大鼠心脏Langendorff灌注模型,分为未处理组、异氟烷组、cheleryth-rine(蛋白激酶C抑制剂)+异氟烷组、chelerythrine组。药物处理(或未处理)后,所有心脏均缺血30min,复灌60min。以Maclab生理实验系统记录心脏的血流动力学指标,HPLC方法测定心肌能量物质含量,免疫印迹方法分析蛋白激酶C(proteinkinaseC,PKC)亚型在细胞内的分布和活性。结果异氟烷明显延缓心肌缺血15min时心肌ATP的耗竭,改善再灌注后的心肌收缩功能以及能量代谢障碍的恢复,增加PKC-δ和-ε亚型的膜转位。PKC抑制剂chelerythrine减少异氟烷诱导的PKC-δ和-ε亚型的膜转位以及心肌功能和ATP的恢复。结论异氟烷延缓心肌缺血期间ATP的耗竭及改善复灌后心肌功能和能量代谢,该保护作用是由PKC介导的。Aim To determine the effects and mechanisms of isoflurane on energy metabolism during ischemia and reperfusion in isolated rat hserts. Methods The rat Langendorff model was used, and isolated perfused rat hearts were separated into untreated, isoflurane, chelerythrine （PKC inhibitor） plus isoflurane, and chelerythrine groups. All the hearts were subjected to treatment before ischemia, followed by 30 min of ischemia and 60 min of reperfusion. Hemodynamic variables were recorded, and metabolites were measured by high-performance liquid chromatography, and analyzed subcellular localization of PKC isoforms by Western blot analysis. Results The recovery of left ventricular developed pressure after ischemia was （33 ± 8 ） %, （56 ± 9 ） %, and （30 -± 5 ）% in the untreated, isoflurane, and isoflurane with chelerythrine groups respectively. Compared with the untreated hearts, isoflurane significantly improved the recovery of left ventricular developed pressure （ P 〈 0. 05 ） , attenuated the depletion of myocardial adenosine triphosphate （ATP） at 15 min of ischemia （6.5 ±1.4 vs. 4.0±0.9, mol·g^-1 wt ; P 〈 0. 05 ） , enhanced the recovery of myocardial ATP concentrations at the end of reperfusion （10.2±0.7 vs. 4.7 ±0.7, mol·g^-1 wt;P 〈0.05）, and was associated with the translocation of PKC-δ and-ε to the membrane. Chelerythrine suppressed the translocation of PKC-δ and-ε and blocked the improvement of cardiac function and ATP. Conclusion Isoflurane delays the consumption of ATP during ischemia and improves the recovery of mechanical function and the energy state 60 min after ischemia. These effects of isoflurane are dependent on the activation of PKC.

关 键 词：异氟烷 蛋白激酶C 能量代谢 心肌缺血 

分 类 号：R-332[医药卫生] R322.11