肝纤维化大鼠的肝素干预治疗观察

Heparin reverses hepatic fibrosis in rats

目的:建立肝纤维化大鼠模型,对肝素的抗肝纤维化疗效进行评价。方法:应用CCl4建立肝纤维化大鼠模型,分别给予不同剂量的肝素进行抗肝纤维化干预治疗。8周后处死大鼠,留取血清检测透明质酸、Ⅳ型胶原、层连蛋白、Ⅲ型前胶原、转化生长因子β1等。留取肝组织,行HE和网织纤维染色,采用免疫组织化学方法检测肝组织中转化生长因子β1的表达,电子显微镜下观察HSC的超微结构变化及狄氏腔内胶原纤维沉积情况。结果:肝素预防性治疗组和肝素治疗组的各项血清学指标水平与肝纤维化大鼠造模组相比,差异均有统计学意义(P<0.001,P<0.01)。网织纤维染色显示,肝素可明显抑制纤维增生。肝素可以降低血清转化生长因子β1水平,与免疫组织化学染色结果一致。电镜下可见肝素治疗后狄氏腔内胶原纤维沉积减少。结论:肝素具有抗肝纤维化作用,其作用机制与抑制转化生长因子β1表达有关。

Objective： To evaluate the effects of heparin on liver fibrosis. Methods： Rats had liver fibrosis induced by carbon tetrachloride. The cirrhotic rats were subjected to different dosages of heparin. All the rats were killed after eight weeks and the serum levels of hyaluronate, collagen type Ⅳ, laminin, precollagen type Ⅲ and TGF-β1 were determined. HE and a reticular fiber staining were used, and the expression of TGF-β1 in liver tissues was measured by an immunohistochemistry. The collagen deposit at Disse space was observed with a scanning electron microscope. Restilts： The serum indexes of heparin preventive treatment group and two heparin treatment groups produced many significant differences in the cirrhotic rats. The result of collagen staining showed that heparin signific＇anfly inhibited fibrosis in rats. The serum concentrations of TGF-β1 in heparin groups were decreased significantly. The collagen in Disse space was less in heparin groups observed with a scanning electron microscope. Condusion： Heparin has anti-fibrosis effects owing to the decrease of TGF-β1 level.