【作者】 孙妩弋；

【导师】 魏伟；

【作者基本信息】 安徽医科大学 ， 药理学， 2005， 硕士

【摘要】 目的:探讨芍芪多苷（SQDG）对卡介苗（Bacillus Calmette Guerin,BCG）加脂多糖（lipopolysaccharide,LPS）诱导的小鼠免疫性肝损伤模型的保护作用及SQDG对人白蛋白致免疫性肝纤维化大鼠模型的抗肝纤维化作用并对其机制作初步研究。同时与有效剂量的白芍总苷（total glucosides of paeony,TGP）或黄芪总皂苷（astragalosides,ASTs）进行药效学比较。 方法:分别建立小鼠免疫性肝损伤模型和人白蛋白致免疫性肝纤维化大鼠模型,分光光度法检测血清中丙氨酸氨基转移酶（alanine aminotransferase,ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase,AST）、一氧化氮（nitric oxide,NO）水平和肝匀浆中丙二醛（malondiadehyde,MDA）、超氧化物歧化酶（superoxide dismutase,SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）、羟脯氮酸（hydroxyproline,Hyp）含量,放免法检测细胞培养上清液中肿瘤坏死因子-α（tumor necrosis factor-alpha,TNF-α）含量,放免法检测血清中透明质酸（hyaluronic acid,HA）和Ⅲ型前胶原（procollagen Ⅲ,PCⅢ）水平,MTT法检测腹腔巨噬细胞（peritoneal macrophages,PMφ）和枯否细胞（kupffer cell,KC）培养上清液中门细胞介素—1（interleukin-1,IL-1）的含量。HE染色法对肝脏组织作病理检查。结果:（1）SQDG(60、120、240mg·kg^-1)灌胃给药能降低免疫性肝损伤小鼠升高的肝脾指数,降低血清中升高的转氨酶水平,病理检查也发现其可明显减轻肝组更多还原

【Abstract】 Objective To investigate the effects of SQDG on Bacillus Calmette Guerin (BCG) plus lipopolysaccharide(LPS)-induced immunological liver injury in mice as well as its possible mechanisms, to study the therapeutic effects and mechanisms of SQDG on immunological hepatic fibrosis induced by human albumin in rats . At the same time the pharmacodynamics of SQDG was compared with total glucosides of paeony (TGP) or astragalosid.es (ASTs) of effective dose.Methods The model of immunological liver injury in mice and immunological hepatic fibrosis induced by human albumin were prepared. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST) , nitric oxide(NO) in serum, malondiadehyde(MDA) content, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) activities in liver homogenate were assayed by spectrophotometry; tumour necrosis factor- α (TNF- α ) activity was determined by ridioimmunoassay; serum hyaluronic acid ( HA) and procollagen III (PC III) were determined by ridioimmunoassay. Liver collagen level was determined by measuring hydroxyproline(Hyp) content in fresh liver samples. The level of interleukin-1 (IL-1)was assayed by MTT dye reduction. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope.Results (1) SQDG (60,120,240mg?kg"’) was able to significantly decrease liver index, spleen index, and decrease serum transaminase (ALT, AST) levels of immunological liver injury’s mice induced by BCG plus LPS, attenuate the area and extent of necrosis and reduce the infiltration of inflammatory cells. Furthermore, SQDG also decreased MDA content and improved the reduced SOD and GSH-Px levels in liver homogenate. Meanwhile, SQDG significantly lowered increased NO level in serum and inhibited the production of TNF-a and IL-1 by peritoneal macrophages. SQDG at the concentrations of 20~80mg ? L"1 were able to inhibit the levels of TNF- a and IL-1 directly produced by KC that induced with LPS. (2) Histological results showed that SQDGC 85 n 170mg ?kg"1) improved the human albumin-induced alterations in the liver structure, alleviated lobular necrosis and significantly lowered collagen content. The anti-fibrotic effects of SQDG also confirmed by decreased serum content of HA and PC III in SQDG-treated group. Moreover, the treatment with SQDG effectively reduced the hydroxyproline content in liver homogenate. However, the levels of ALT and AST increased in fibrotic rats but had no significance compared with normal control, whereas the ratio of A/G decreased also had no significance. SQDG had no effect on level of ALT ,AST and the ratio of A/G. Furthermore, SQDG treatment significantly blocked the increase in MDA, associated with a partially elevation in liver total antioxidant capacity including SOD and GSH-Px. (3) Comparing with TGP and ASTs. SQDG significantly further changed the serum transaminase levels, MDA production while had no difference effects on other indices.Conclusion SQDG possesses protective action on immunological liver injury in mice, which was related to direct with free radical scavenging, increasing the content of SOD and GSH-Px, immunoloregulation and so on. Meanwhile, SQDG have beneficial effects on hepatic fibrosis in rats by inhibition of collagen synthesis, decreasing oxidative更多还原