【摘要】 目的研究鬼针草总黄酮(TFB)对日本血吸虫病小鼠肝组织α平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGFβ1)、Ⅰ型胶原、金属蛋白酶组织抑制因子-1(TIMP-1)蛋白表达的影响,探索鬼针草总黄酮抗血吸虫病肝纤维化的作用机制。方法以日本血吸虫尾蚴感染BalB/C小鼠制作肝纤维化动物模型,6周末随机分为TFB高剂量组(230mg/kg·d-1)、中剂量组(115mg/kg·d-1)、低剂量组(57.5mg/kg·d-1)和阳性对照组(秋水仙碱0.15mg/kg·d-1)和模型组,各组均于感染42d后用吡喹酮(400mg/kg·d-1)治疗1d,同时设置正常对照组10只。感染14周后处死,放射免疫法测定血清透明质酸(HA)的含量,碱水解法测定肝组织羟脯氨酸(Hyp)含量,用免疫组织化学方法评价α-SMA、TGFβ1、Ⅰ型胶原、TIMP-1的表达情况。结果TFB高、中剂量组与模型组相比较,肝组织α-SMA、TGFβ1、TIMP-1表达及Hyp含量均显著降低(P<0.01),TFB低剂量组与模型组比较差异无显著性(P>0.05);TFB高剂量组与模型组相比较,Ⅰ型胶原蛋白表达量显著降低(P<0.01),TFB中、低剂量组与模型组比较差异无显著性(P>0.05);TFB高、中、低剂量组与模型组相比较,血清HA含量均显著降低(P<0.01)。结论高剂量TFB显著降低血吸虫病小鼠肝组织α-SMA、TGFβ1、Ⅰ型胶原、TIMP1表达,其抗血吸虫病肝纤维化作用机制与抑制肝星状细胞活化及胶原合成有关。更多还原

【Abstract】 Objective To study the mechanisms of total flavones Bidens Pilosa L(TFB) on hepatic fibrosis in mice with Schistosomiasis japonica.Methods Fifty Balb/c mice were infected with cercarie of Schistosoma japonicum. The infected mice were divided randomly into five groups at the end of the 6 th week after infection:model group,high dose TFB group (230 mg/kg·d-1),middle dose TFB group (115 mg/kg·d-1),low dose TFB group (57.5 mg/kg·d-1) and anti-hepatic fibrosis drugs (Colchicines) group (0.15 mg/kg·d-1) as positive drug control group,forty two days after infection,the five groups were treated with Praziquantel (400 mg/kg·d-1) for one day. Ten healthy Balb/C mice were used in this experiment as normal control group. All animals were sacrificed at the end of the 14th weeks,serum hyaluronic acid (HA) was detected with radioimmunoassay,the content of hydroxyproline (Hyp) in live tissues was tested by specimen alkaline hydrolysis,the expression levels of α-smooth muscle actin(α-SMA),transforming growth factor β1 (TGF-β1),tissue inhibitor of metalloproteinase-1 (TIMP-1) and collagen type Ⅰ were measured by immunohistochemical method.Results high and middle dose TFB groups significantly relieved the content of hydroxyproline and reduced the levels of α-SMA,TGF-β1 and TIMP-1 in hepatic tissues compared with model group(P<0.01),there were not any differences in all the above parameters between low dose TFB group and model group(P>0.05) ;the expression levels of collagen type Ⅰ protein of high dose TFB group were significantly lower than those in model group (P<0.01),but there was no significant difference between middle,low dose TFB group and model group(P>0.05). The content of serum hyaluronic acid in all TFB group was significantly lower than that in model group (P<0.01).Conclusion High dose TFB treatment significantly reduces the expression levels of α-SMA,TGF-β1,TIMP-1 and collagen type Ⅰ,which exerts its effects on hepatic fibrosis in mice with Schistosomiasis japonica by inhibiting activation of hepatic stellate cell and synthesis of collagen.更多还原