肝络通对门静脉高压症大鼠肝组织纤维化的影响

Effect of Glytan on Liver Fibrosis in Portal Hypertensive Rats

目的:观察肝络通对门静脉高压症大鼠肝纤维化程度的影响,探讨肝络通治疗门静脉高压症的作用机制。方法:取体重250±10 g的清洁级SD雄性大鼠105只,根据体重随机分为假手术组、模型组、心得安组、肝络通组。采用胆总管结扎的方法制作胆汁性肝纤维化门静脉高压症模型。术后2周和4周分别测定各组大鼠肝组织羟脯氨酸的含量,采用Masson染色和透射电镜的方法观察肝组织形态学的变化。结果:肝络通在2周和4周均能显著抑制肝组织羟脯氨酸的合成,且心得安在4周可减少羟脯氨酸的含量。Masson染色显示肝络通显著抑制纤维增生,且缓解肝组织结构紊乱。透射电镜的结果显示,模型组大鼠星状细胞活化、增殖,肝窦内皮细胞窗空减少,内皮细胞下纤维组织增生,肝窦毛细血管化;Disse间隙内肝细胞微绒毛减少或消失。肝络通组Disse间隙可见大量的微绒毛,肝窦内皮细胞窗空清晰可见。结论:肝络通可显著抑制胶原的合成,改善肝窦毛细血管化,阻逆肝纤维化进程,这是肝络通降低门静脉压力的机制之一,同时为开发作用靶点清晰的降低门静脉压力的药物提供了丰富的药理学资料。

This research was aimed to observe the effect of Glytan on rat liver fibrosis and investigate the mechanism of portal hypertension（PHT）.SD male rats with the weight between 240 g to 260 g,were randomly divided into sham group,model group,propranolol group,and Glytan group according to weight.PHT and liver fibrosis were induced by common bile duct ligation.After 2 and 4 weeks,hydroxyproline（Hyp） content of liver tissues was tested by spectrophotometer.The collagen formation was evaluated by Masson staining and ultrastructural changes by transmission electron microscopy（TEM）.The results showed that Glytan inhibited Hyp production at 2 and 4 weeks.Masson staining revealed the same results with Hyp.Glytan inhibited pseudolobule formation.TEM showed swelling sinusoid endothelial cells（SEC）,reduced fenestra between SEC,widened Disse space,reduced hepatocyte microvilli in model group rats.At 4 weeks,loss of hepatocyte microvilli and basement membrane were clearly seen.Glytan promoted degeneration of matrix and restoration of SEC at 2 and 4 weeks.It was concluded that Glytan inhibited collagen formation and ameliorated sinusoidal capillarization.This is one of the mechanisms of Glytan decreases portal venous pressure.The results provided precise and reliable proof to develop new treatment for PHT.