中国中药杂志

2001, (09)

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黄芪总黄酮对扑热息痛所致肝损伤的防护机理探讨
Protection Against Paracetamol induced Hepatic Damage Using Total Flavonoids of Astragalus

汪德清,Critchley Julian AJH,丁保国,马艳青,赵海潞,Thomas G Neil,田亚平,Tomlinson B rian,Critchley Lester AH,James Anthony Edward
WANG De qing 1,2 , CRITCHLEY Julian AJH 1, DING Bao Guo 1, MA Yan qing 1, ZHAO Hai lu 1, THOMAS G Neil 1, TIAN Ya ping 2, TOMLINSON Brian CRITCHLEY Lester AH 3, James Anthony Edward 4 (1.Division of Clinical Pharmacology, Department o

摘要(Abstract):

目的 :研究黄芪总黄酮对扑热息痛所致肝损伤的防护机理。方法 :用高压液相测定扑热息痛及代谢产物和苯巴比妥诱导睡眠模型研究黄芪总黄酮 (TFA)对扑热息痛的代谢及TFA抗扑热息痛所致损伤的机理。结果 :TFA可明显降低尿中硫醚胺酸的浓度 ,其变化与TFA浓度成反比 ;但对其它代谢产物的影响无明显统计学差异。苯巴比妥诱导小鼠睡眠实验结果显示 ,TFA (10 0mg·kg-1)本身对苯巴比妥代谢无明显影响 (P >0 .0 5 ) ,扑热息痛 (40 0mg·kg-1)可显著延长小鼠的睡眠时间 (P <0 .0 0 1) ;但TFA (10 0mg·kg-1)明显缩短扑热息痛所延长的苯巴比妥诱导的睡眠时间 (P <0 .0 0 5 )。结论 :TFA抗扑热息痛损伤的作用机理可能与TFA抑制扑热息痛某些代谢过程以及降低扑热息痛代谢过程中产生毒性代谢产物有关
Objective:To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol induced hepatic damage. Method: Analysing paracetamol and its metabolites in mice urine by HPLC and studying the mechanism of anti damage induced by paracetamol using experiment module of pentobarbital induced sleeping time. Result:Administration of large doses of paracetamol to C57BL/6J mice produced significant hepatic injury with marked elevation in serum ALT activity and severe hepatocellular necrosis. TFA showed a good protective capability against paracetamol induced hepatic injury. TFA had no marked effect on paracetamol and its metabolites except for the mercapturate conjugate. The concentration of mercapturate change decreased with increasing TFA dose. TFA had no effect on the pentobarbital metabolites ( P >0.05). However, paracetamol (400mg·kg -1 ) prolonged the sleeping time (by 110 min relative to the controls, P <0.001). The TFA ( P <0.005) caused significant reduction in paracetamol prolonged pentobarbital induced sleep. Conclusions: The mechanism of TFA's protective effect against the paracetamol induced damage may be related to the inhibition of some metabolism progress of paracetamol and the reduction of the toxicity metabolite such as mercapturate conjugate.

关键词(KeyWords): 黄芪总黄酮;扑热息痛;苯巴比妥
total flavonoids of Astragalus; paracetamol; pentobarbital

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基金项目(Foundation): 香港特区科学基金 (RGC,4134/0 0M )

作者(Author): 汪德清,Critchley Julian AJH,丁保国,马艳青,赵海潞,Thomas G Neil,田亚平,Tomlinson B rian,Critchley Lester AH,James Anthony Edward
WANG De qing 1,2 , CRITCHLEY Julian AJH 1, DING Bao Guo 1, MA Yan qing 1, ZHAO Hai lu 1, THOMAS G Neil 1, TIAN Ya ping 2, TOMLINSON Brian CRITCHLEY Lester AH 3, James Anthony Edward 4 (1.Division of Clinical Pharmacology, Department o

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