【作者】 路景涛；

【导师】 陈敏珠； 杨雁；

【作者基本信息】 安徽医科大学 ， 药理学， 2003， 硕士

【摘要】 复方黄芪提取物（compound astragalus extract，简称CAE）是复方黄芪的有效部位群，主要含有四个活性部分（P_a、P_b、P_c、P_d）。本文分别在体内、外对CAE的保肝作用及其机理进行了初步研究，并对CAE四个部位的活性强度进行了比较。主要内容概括如下： 1．CAE对小鼠D-Gal N性肝损伤的保护作用 采用D-半乳糖胺(D-GaIN，800mg·kg^-1，ip)诱导小鼠急性肝损伤模型。实验结果表明，CAE三个剂量(60，120,240 mg-kg^-1，ig)均能明显降低D-GalN升高的肝脏指数、血清ALT水平及肝匀浆MDA的含量，提示，CAE对小鼠急性D-GalN性肝损伤有明显的保护作用，作用机理可能与其抗炎及抗氧化作用有关。 2．CAE对BCG+LPS诱导小鼠免疫性肝损伤的保护作用 采用卡介苗（BCG，1×10⁷/0.2ml，iv）+脂多糖(LPS，7.5ug/0.2ml,d₁₂，iv)诱导小鼠免疫性肝损伤模型。实验结果表明，CAE中、高(120,240 mg·kg^-1，ig)明显降低免疫性肝损伤小鼠升高的血清ALT水平、肝脏指数；明显上调小鼠低下的脾细胞ConA增殖反应；对BCG+LPS升高的小鼠PM_φ产生IL-1及TNF_α有明显的下调作用，提示，CAE对小鼠免疫性肝损伤有明显的保护作用，作用机理可能与其免疫调节及抗炎作用有关。 3．CAE体外对大鼠腹腔巨噬细胞功能的抑制作用 CAE(11.3～90 mg·L_<sup>-1)体外对LPS诱导大鼠PM_φ产生NO、TNF_α与IL-1均有明显的抑制作用。提示CAE可能通过抑制大鼠巨噬细胞的功能而发挥其抗肝损伤作用。 4．CAE四个有效部位活性强度的比较安徽医科大学硕士学位论文 CAE四个有效部位均能明显降低LPS刺激大鼠PM。产生IL一1、TNF。与NO。以ICS。比较各部位抑制大鼠PM。产生IL一1与NO的作用强度顺序为Pd>Pb>Pc>Pa、抑制大鼠PM。产生TNF。的作用强度顺序为Pd>Pb>Pa>P。。提示，CAE四个部位均为其活性部位，但活性强度不同。 上述体内、外的实验结果表明，CAE对小鼠D一GalN性肝损伤和免疫性肝损伤均有明显的保护作用;体外对大鼠PM。分泌炎性因子一TNF。、IL一1与NO均有明显的抑制作用。CAE的四个活性有效部位（P。、Pb、P。、Pd）对大鼠腹腔巨噬细胞的上述功能均有明显的抑制作用，但活性强度不同。提示，CAE抗肝损伤的作用机制可能与下列作用有关（l）抗炎作用并可直接抑制巨噬细胞分泌炎性因子;（2）增强机体的抗氧化能力，降低脂质过氧化物水平;（3）免疫调节作用。更多还原

【Abstract】 Compound astragalus extract (CAE) is composed of active parts(Pa, Pb, Pcand Pa). In this study,the hepatoprotective effect of CAE and its mechanism of action was investegated in vivo and in vitro.Furthermore,we compared activities of the fuor parts of CEA. The main contents are as follows :1. Protective effect of CAE on D-galactosamine-induced liver injury in miceAcute liver damage model induced by D-galactosamine (D-GalN,800 mg-kg-1,ip) in mice was used in this study.The results showed that CAE (60,120 and 240 mg-kg-1,ig) could obviously lowen the elevated liver index, ALT level in serum and MDA content in liver homogenate of mice treated with D-GalN. This suggested that CAE had protective effect on D-GalN-induced acute liver injury significantly, probably being related to its anti-inflammatory and anti-oxidative effect.2. Protective effect of CAE on BCG+LPS-induced immunological liver injury in miceBCG+LPS-induced liver injury model was successlly duplicated, the results showed that CAE (120 , 240 mg-kg-1,ig) could markedly lowen the elevated ALT activity in serum and liver index, restore the diminished proliferative response of splenocyte induced by ConA and decrease the elevated IL-1, TNFa production of peritoneal macrophages from BCG+LPS treated mice. This suggested that CAE had protective effects on BCG+LPS-induced immunological liver injury significantly, probably being related to its immunomodulatory and anti-inflammatory effect.3. Inhibitory effect of CAE on function of peritoneal macrophages from normal rats in vitro.In order to find out the mechanism of the heoatoprotective effects,its effect on thefunction of peritoneal macrophages from normal rats was studied in vitro.Our results showed that CAE(11.3-90 mg-L-1) could markedly inhibit LPS-induced production of NO, TNF and IL-1 of PMS from normal rats.This suggested that CAE has direct inhibitory effect on the function of activated rat M s.4. Comparison of activities of the four parts of CAE.We also compared the effect of four parts of CAE(Pa ,Pb ,PC and Pd) on the secretory function of PM S from normal rats in vitro.The results showed that four parts of CAE all could lowen NO, TNFa and IL-1 productions of PM S induced by LPS from normal rats.The order of their inhibtory action to IL-1 and NO is Pd>Pb>Pc>Pa evaluated by IC50;and that to TNFa is Pd>Pb>Pa>Pc -This suggested that the four parts of CAE are all active,however their activities were different.On conclusion, these results indicated that CAE has markedly protective effect on D-GalN induced liver injury and immunological liver damage in mice. CAE also has inhibitory effect on the secretion of inflammatory factor such as TNFa, IL-1 and NO of PM ,from normal rats in vitro. Moreover,four parts of CAE(Pa ,Pb ,PC and Pd) all have inhibitory effect on function of PM stated above.The order of their activities to IL-1 and NO isPd>Pb>Pc>Pa evaluated by IC50, and that to TNF is Pd>Pb>Pa>Pc .These suggested that the heoatoprotective effect of CAE might be related to these as follows: l)anti-inflammatory effect and inhibiting inflammatory factors secretion of PMS directly; 2) enhancing anti-oxidative function and decreasing lipid peroxidation level; 3) immunomodulatory effect.更多还原