肝络通对门静脉高压症大鼠肝组织纤维化的影响

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.     

Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats

AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats.METHODS:Glytan(Ganluotong in Chinese),is composed of salvianolic acid B and diammonium glycyrrhizinate.Portal hypertension(PHT)was induced in the rats by common bile duct ligation(BDL).Hemodynamic studies were performed using the colored microsphere method.Radioimmunoassay(RIA)was used to determine endothelin(ET)-1 levels in the mesenteric circulation.Western blotting methods were used to investigate the effect of Glytan on ET A receptor(ETAR),ET B receptor(ETBR),endothelial NO synthase(e NOS),G-protein-coupled receptor kinase(GRK)2,and β-arrestin 2 expression in the mesentery.The m RNA of ETAR and ETBR was determined using real-time polymerase chain reaction.RESULTS:Treatment with Glytan reduced portal pressure(PP)and portal territory blood flow(PTBF)and increased both mean arterial pressure(MAP)and splanchnic vascular resistance(SVR).Especially at 4wk,PP decreased by about 40%,while MAP increased by 13%,SVR increased by 12%,and PTBF decreased by about 21%.The effect of blood flow reduction was greatest in the mesentery(about 33%)at 4 wk.The mesenteric circulation ET-1 levels of BDL rats were lower and negatively correlated with PP at 4 wk.Glytan can increase mesenteric ET-1 content and inhibit ETBR,e NOS,GRK2,andβ-arrestin 2 expression in the mesentery.Moreover,Glytan showed no effect on the expression of ETAR protein and m RNA.CONCLUSION:The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.     

肝络通对门静脉高压症大鼠内脏血流动力学的影响

目的:观察肝络通对门静脉高压症大鼠内脏血流动力学的影响。方法:应用胆总管结扎的方法制作胆汁性肝硬化门静脉高压症模型。大鼠分为假手术组、模型组、肝络通组。2周后灌胃给药,4周后取材。采用插管的方法测定门静脉压力和平均动脉压力。采用彩色微球技术,测定内脏各组织的血流量、内脏循环血流阻力、门区血流量。结果:治疗后,肝络通可有效降低门静脉压力,升高体循环平均动脉压力,降低门区血流量,提高内脏循环阻力。在降低内脏血流量方面,以降低肠系膜和小肠的血流量作用最为显著。结论:肝络通可有效缓解门静脉高压症高动力循环,这是肝络通降低门静脉压力的机制之一。     

肝络通防治大鼠胆汁性肝纤维化门静脉高压症的初步研究

目的:探讨肝络通降低胆汁性肝纤维化引起的大鼠门静脉高压的作用机制。方法:取体质量240-260g左右的清洁级SD雄性大鼠156只,根据体质量随机分为假手术组、模型组、心得安组、肝络通高、中、低剂量组。采用胆总管结扎的方法造成大鼠胆汁性肝纤维化模型。术后2周和4周分别测定各组的门静脉压力,HE染色观察肝组织学的变化,检测血清肝功能,放免法定量体循环和肠系膜上动脉血浆内皮素-1的浓度。结果:术后2周和4周,模型组大鼠门静脉压力显著升高。心得安和肝络通在两个时间点有显著的降压作用。肝络通能显著抑制胶原生成,促进肝组织结构的恢复;肝功能显示肝络通在两个时间点均能显著降低血清丙氨酸氨基转移酶(AST)、门冬氨酸氨基转移酶的活性(ALT),血清总蛋白(TP)、白蛋白(ALB)、总胆红素(TBIL)的含量和Na+的浓度。门静脉高压症初期肝络通降低体循环内皮素-1的浓度,提高肠系膜循环的内皮素-1的浓度,抑制内脏血管的舒张。结论:肝络通通过改善肝功能,抑制胶原生成,调节肝内微循环,改善纤维化初期高动力循环,抑制水钠潴留,从而降低门静脉压力。