摘要
目的 研究双环醇对扑热息痛 (对乙酰氨基酚 )引起小鼠肝能量代谢紊乱和线粒体功能障碍的保护作用。方法 小鼠ip扑热息痛 12 0mg·kg- 1 引起急性肝损伤 ,观察血清谷丙转氨酶 (ALT)和谷草转氨酶 (AST)水平、肝活体磷谱、肝线粒体膜流动性及线粒体ATPase活性的改变。结果 双环醇可显著抑制扑热息痛中毒小鼠PME ATP及PME PDE的升高。双环醇 (2 0 0mg·kg- 1 )可显著降低扑热息痛导致的线粒体膜流动性下降 ,并对线粒体ATPase活性降低有显著保护作用。结论 双环醇可保护扑热息痛导致的急性肝损伤 ,使肝脏能量代谢和磷脂代谢趋于正常 。
AIM To investigate the mechanism of the protective effect of bicyclol on acetaminophen induced hepatotoxicity in mice. METHODS 31 P MRS spectra in vivo were determined by using surface coil technique. The membrane fluidity of mitochondria and the activity of mitochondrial ATPase were also determined by spectrofluorophotometry and spectrophotometry methods. RESULTS The hepatotoxicity of acetaminophen is related to the lipid peroxidation and covalent binding to macromolecules, which leads to damage of mitochondrial function. Our results showed that the decrease of ATP/Pi and the elevation of PME/ATP in acetaminophen intoxicated mice were significantly inhibited by two doses of bicyclol (100, 200 mg·kg -1 ) pretreatment, which indicate that bicyclol has significant protective effect on the decrease of liver ATP content induced by acetaminophen. Acetaminophen significantly inhibited the activity of mitochondrial ATPase by its cytotoxic metabolite NAPQI [ N acetyl p benzoquinone], which has the potential to react with sulfhydryl groups or through sulfhydryl group oxidation. Our results showed that the reduction of mitochondrial fluidity as well as the inhibitory effect of mitochondrial ATPase induced by acetaminophen were also reduced by bicyclol. CONCLUSION The effect of bicyclol on acetaminophen induced liver injury maybe partly due to its protective effects on hepatic energy metabolism and mitochondria function.
出处
《药学学报》
CAS
CSCD
北大核心
2001年第10期723-726,共4页
Acta Pharmaceutica Sinica
关键词
双环醇
扑热息痛
NMR
^31P
线粒体
能量代谢
bicyclol
acetaminophen
magnetic resonance spectroscopy
mitochondria
energetic metabolism
