Satoh K, Nakai T, Ichihara K
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Eur J Pharmacol. 1994 Aug 3;270(4):365-9. doi: 10.1016/0926-6917(94)90014-0.
Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was induced by cessation of the systemic circulation for 60 min. Liver mitochondria were isolated and the respiration was determined by polarography using glutamate and succinate as substrates. In the vehicle-treated group, ischemia drcreased ZO3, respiratory control index (RCI: QO3/QO4), and ADP/O ratio. Pretreatments with pravastatin and simvastatin enhanced the decreases in QO3 measured with either glutamate or succinate, and in ADP/O ratio measured with succinate. Because of decreasing QO4, HMG-CoA reductase inhibitors did not modify the changes in RCI due to ischemia. There were no significant differences in respiratory indices between pravastatin- and simvastatin-treated groups. In conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of liver mitochondria under pathophysiological conditions, such as ischemia.
研究了3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂普伐他汀和辛伐他汀对缺血大鼠肝脏线粒体呼吸的影响。每天口服溶剂、普伐他汀（2或4mg/kg）或辛伐他汀（1或2mg/kg），持续3周。通过停止体循环60分钟诱导肝脏缺血。分离肝脏线粒体，以谷氨酸和琥珀酸为底物，用极谱法测定呼吸。在溶剂处理组中，缺血降低了细胞色素氧化酶（ZO3）、呼吸控制指数（RCI：QO3/QO4）和ADP/O比值。普伐他汀和辛伐他汀预处理增强了用谷氨酸或琥珀酸测定的QO3以及用琥珀酸测定的ADP/O比值的降低。由于QO4降低，HMG-CoA还原酶抑制剂未改变缺血引起的RCI变化。普伐他汀和辛伐他汀处理组之间的呼吸指标无显著差异。总之，HMG-CoA还原酶抑制剂可能会在病理生理条件下，如缺血时，增强肝脏线粒体的呼吸损伤。
