【作者】 朴娟玉；

【导师】 南极星；

【作者基本信息】 延边大学 ， 生药学， 2009， 硕士

【摘要】 目的研究高山红景天多酚对小鼠肝损伤的作用。方法健康昆明种雄性小鼠随机分成6组:1)正常对照组;2)模型组;3)高山红景天多酚低剂量组;4)高山红景天多酚中剂量组;5)高山红景天多酚高剂量组;6)水飞蓟素阳性对照组。小鼠急性肝损伤模型分别通过腹腔注射D-氨基半乳糖(D-galactosamine,D-GalN)700 mg/kg联用脂多糖(Lipopolysaccharide,LPS)10μg/kg,腹腔注射对乙酰氨基酚(Acetaminophen,APAP)300 mg/kg,灌胃他克林(Tacrine,THA)35 mg/kg来分别制备。给药组在造模前第24h,12h,1h(2h)时分别灌胃高山红景天多酚(50,100,150 mg/kg),水飞蓟素(100 mg/kg),其他组给予相同体积的生理盐水。小鼠的肝损伤主要由血清指标丙氨酸氨基转化酶(ALT)、天冬氨酸氨基转化酶(AST)、肿瘤坏死因子(TNF-α)和组织中丙二醛(MDA)、谷胱甘肽(GSH)等水平来进行评价。并且用组织病理学和免疫组织化学方法观察每组肝组织病理变化及caspase-3和缺氧诱导因子(HIF-1α)的表达。结果D-GalN/LPS,APAP,THA可以诱导小鼠肝损伤,主要表现在小鼠血清ALT、AST水平的显著升高和肝组织MDA水平和GSH消耗的显著升高。并且肝组织发生严重的病理变化,也表达caspase-3和缺氧诱导因子-1α(HIF-1α)。提前给予高山红景天多酚不但可以减轻由D-GalN/LPS,APAP,THA诱导的肝组织病变程度和caspase-3和HIF-1α的表达,还显著降低小鼠血清中的ALT、AST水平,组织中的MDA水平和GSH的消耗。结论高山红景天多酚对D-GalN/LPS,APAP,THA诱导的小鼠肝损伤具有保护作用,其作用其机制可能是与清除自由基,抗氧化,抑制caspase-3和HIF-1α表达有关。更多还原

【Abstract】 Objective To investigate the effect of Rhodiola sachalinensis polyphenol (RSP) on liver injure induced by D-galactosamine(D-GalN)/Lipopolysaccharide(LPS), Acetaminophen(APAP),Tacrine(THA) in mice.Methods Healthy male Kunming mice were randomly divided into 6 groups:Normal group,Model group,RSP groups(50,100,150 mg/kg,respectively),Silymarin groups(100 mg/kg).Mice were pretreated with RSP or Silymarin by orally,at 24h,12h and 1h(2h) before D-GalN/LPS,APAP,THA injection and sacrificed after 8h or 12h or 6h treated with D-GalN/LPS,APAP,THA.The liver accessed biochemically and histologically.To observe serum alanine aminotransferase(ALT),aspartate amino transferase(AST) and hepatic malondialdehyde(MDA),glutathione(GSH) et al.Furthermore, histopathological and immunohistochemical were performed after hematoxylin & esosin (H&E) staining and caspase-3,hypoxia-inducible transcription factor-1α(HIF-1α) staining.Results D-GalN/LPS,APAP,THA could induce liver injury by markedly increase serum ALT,AST,the haptic MDA and GSH depletion.Also significantly increase the histopathology change and caspase-3 or HIF-1αexpression in mice liver. Pretreated with RSP markedly reduced the leather liver injury and the expression of caspase-3 or HIF-1αin the experimental animals and significantly decrease ALT,AST and the haptic MDA.Furthermore RSP pretreatment also significantly alleviated the hepatic GSH.Conclusion These results suggest that RSP have protective effect on D-GalN/LPS,APAP,THA induced liver injury in mouse model,the potential mechanism was related on remove free radicals,antioxidation and inhibit the caspase-3, HIF-1αexpression.更多还原