芍芪多苷抗大鼠免疫性肝纤维化作用及部分机制

目的探讨芍芪多苷(SQDG)抗大鼠免疫性肝纤维化的作用并对其机制作初步研究。方法建立人白蛋白致免疫性肝纤维化大鼠模型,设立正常对照组、模型组、SQDG给药组(42.5、85、170mg.kg-1)和阳性对照秋水仙碱组(Col0.1mg·kg-1)。HE染色对肝脏组织作病理检查。分光光度法检测血清中转氨酶活性和肝匀浆中丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性、羟脯氨酸(Hyp)含量;放免法检测血清中透明质酸(HA)、Ⅲ型前胶原(PCⅢ)水平;3H-Pro参入法检测SQDG对转化生长因子-β1(TGF-β1)刺激的肝星状细胞(HSC-T6)胶原合成的影响。结果SQDG对升高的血清转氨酶有降低趋势,但差异无显著性;病理组织学检查发现,SQDG可降低免疫性肝纤维化大鼠的纤维化程度,与模型组相比,纤维沉积、肝小叶的破坏等均有所减轻。SQDG还可降低肝纤维化大鼠肝组织Hyp含量,降低血清中HA和PCⅢ含量。进一步研究发现,SQDG降低肝纤维化大鼠肝匀浆中MDA的含量,升高抗氧化酶SOD、GSH-Px活性,改善肝脏氧化状态。SQDG(20～160mg·L-1)体外给药还可明显降低HSC-T6的3H-Pro参入量。结论SQDG具有明显的抗肝纤维化作用,其机制可能与其清除自由基、提高抗氧化物酶的活性和抑制HSC的胶原合成有关。

Effects and mechanisms of Shaoqiduogan on immunological hepatic fibrosis

Aim To investigate the effects of Shaoqiduogan(SQDG)on immunological hepatic fibrosis induced by human albumin in rats as well as its possible mechanisms.Methods The model of immunological hepatic fibrosis induced by human albumin was prepared.The rats were randomly divided into 6 groups,namely normal control group,liver fibrosis model group,SQDG(42.5,85,170 mg·kg~(-1))treated groups and colchicine(0.1 mg·kg~(-1)) treated group.HE staining was used to examine the histopathological change.The activities of transaminase in serum,malondiadehyde(MDA)content,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activities,hydroxyproline(Hyp)content in liver homogenate were assayed byspectrophotometry.The levels of hyaluronic acid(HA)and procollagen Ⅲ (PCⅢ)in serum were determined by radioimmunoassay.In vitro,the collagen production of hepatic stellate cell(HSC)-T6 stimulated with transforming growth factor beta1(TGF-β1)was measured with 3H-Proline uptake.Results SQDG had obvious protective effects on human albumin induced hepatic fibrosis in rats.The results showed that the serum ALT and AST decreased by SQDG treatment,but had no significant difference compared with model group.Pathological examination showed that SQDG could remarkably alleviate the hepatic fibrosis.SQDG not only decreased the Hyp content in liver homogenates,but also the elevated level of HA,PCⅢ in serum.SQDG also ameliorated the oxidative stress state of hepatic fibrosis rats,decreased the production of MDA and enhanced the activities of antioxidative enzyme including SOD and GSH-Px.Furthermore,SQDG(20～160 mg·L~(-1))inhibited the collagen production of HSC stimulated with TGF-β1 in vitro.Conclusion sSQDG has protective effect on liver fibrosis rats induced by human albumin.The mechanisms of its anti-fibrotic effects may be associated with its action of ameliorating the oxidative stress in liver,and inhibiting the production of collagen in HSC.