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郑青山,徐列明,仝欣,孙明瑜,宁冰冰,陆雁,刘平,刘佳,刘成海,李医明,李风华,胡义扬,陈高峰.基于均匀设计分析黄芪汤活性组分抗二甲基亚硝胺大鼠肝纤维化的配伍作用[J].,2011,31(10):1389-1393
基于均匀设计分析黄芪汤活性组分抗二甲基亚硝胺大鼠肝纤维化的配伍作用
Uniform Designed Research on the Active Ingredients Assembling of Huangqi Decoction for Inhibition of DMN-induced Liver Fibrosis
  
DOI:
中文关键词:  肝纤维化  均匀设计  黄芪汤  中药组分配伍
英文关键词:cirrhosis  uniform design  Huangqi Decoction  combination components
基金项目:国家重点基础研究发展计划项目资助(973计划,No.2006CB504801);国家自然科学基金重大研究计划重点项目(No.90409020);上海市医学领军人才项目资助(No.2007A卫01)
Author NameAffiliation
郑青山 上海中医药大学附属曙光医院 
徐列明 上海中医药大学附属曙光医院 
TONG Xin 上海中医药大学附属曙光医院
上海市中医药研究院肝病研究所
肝肾疾病病证教育部重点实验室(上海中医药大学)上海高校中医内科学E研究院 
孙明瑜 上海中医药大学附属曙光医院 
宁冰冰 上海中医药大学附属曙光医院
上海市中医药研究院肝病研究所
肝肾疾病病证教育部重点实验室(上海中医药大学)上海高校中医内科学E研究院 
LU Yan 上海中医药大学附属曙光医院
上海市中医药研究院肝病研究所
肝肾疾病病证教育部重点实验室(上海中医药大学)上海高校中医内科学E研究院 
刘平 上海中医药大学附属曙光医院 
刘佳 上海中医药大学附属曙光医院
上海市中医药研究院肝病研究所
肝肾疾病病证教育部重点实验室(上海中医药大学)上海高校中医内科学E研究院 
刘成海 上海中医药大学附属曙光医院 
李医明 上海中医药大学 
李风华 上海中医药大学 
胡义扬 上海中医药大学附属曙光医院 
CHEN Gao-feng 上海中医药大学附属曙光医院
上海市中医药研究院肝病研究所
肝肾疾病病证教育部重点实验室(上海中医药大学)上海高校中医内科学E研究院 
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中文摘要:
      目的筛选古典方剂黄芪汤抗肝纤维化的有效组分及配伍作用。方法 (1)4周内给大鼠腹腔注射二甲基亚硝胺(dimethylnitrosamine,DMN)12次制备肝纤维化模型,于造模第3周首日开始给药干预至4周末。采用均匀设计对黄芪汤中4种组分(分别为黄芪总皂苷、黄芪总黄酮、甘草酸、甘草总黄酮)以4因素8水平安排给药;以肝组织羟脯氨酸(Hyp)含量和丙氨酸氨基转移酶(ALT)活性为观测指标,采用逐步回归法分析其抗肝纤维化效应的最优组方。(2)组分复方的再验证:模型制备及给药方法同上,采用上述实验获得的组分复方,与原方对照,观测大鼠肝组织胶原染色、Hyp含量及血清肝功能等变化。结果通过均匀设计研究,确定最优组方为组分复方(黄芪总皂苷、甘草酸的配伍比例为164:48),并得到有效验证。与模型组比较,组分复方及黄芪汤均可显著改善肝纤维化病理组织学变化,显著降低肝组织Hyp含量、血清ALT、天冬氨酸氨基转移酶(AST)以及碱性磷酸酶(ALP)活性(P<0.05);组分复方在降低肝组织Hyp含量及降低血清ALT活性方面均优于其分别单用组(P<0.05),降低血清ALT活性的作用优于黄芪汤原方(P<0.05)。结论黄芪总皂苷和甘草酸是黄芪汤发挥抗DMN大鼠肝纤维化作用的有效组分;两个组分配伍在降低肝组织胶原沉积及降低血清ALT活性方面具有明显的协同效应。
英文摘要:
      Objective To screen out effective ingredients of Huangqi Decoction(HQD) on dimethylnitrosamine(DMN) induced liver fibrosis and its assembling actions.Methods(1) DMN solution(0.5%) was peritoneally injected to rats to prepare the liver fibrosis model for 12 times,starting from the 1st day of modeling to the end of the 4th week.Uniform design method with 4-factor 8-level table was used to optimize the proportion of four ingredients from HQD,including astragalosides(AS),astragalus flavonoids(AF),glycyrrhizae acid(GA),and glycyrrhizae flavonoids(GF).Moreover,the changes of hydroxyproline(Hyp) content in the liver issue and the level of alanine aminotransferase(ALT) in serum were observed as screen indices,and the method of regression analysis was used to find out an optimal combination.(2) A further study for comparing and verifying the efficacy of the obtained optimized prescription was conducted by observing the changes of fibrosis pathology,the content of Hyp in the liver tissue and serum enzyme activity after medication.Results The optimal proportion of AS and GA was 164:48.Compared with the model group,the content of Hyp in the liver tissue and the levels of ALT,aspartate aminotransferase(AST),and alkaline phosphatase(ALP) in serum decreased significantly,indicating the inhibiting effect of HQD and the AS/GA combination group on hepatic fibrosis formation(P<0.05).The AS/GA combination group was better than AS/GA used alone group in reducing the content of Hyp in the liver tissue and the level of ALT in serum.Furthermore,the AS/GA combination group was better than the HQD group in reducing the level of ALT in serum.Conclusions AS and GA were effective ingredients of HQD,and the combination of AS and GA had obvious synergistic effect in reducing liver collagen deposition and decreasing serum ALT activity in DMN-induced liver fibrosis.
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