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目的探讨通过构建针对大鼠肝星状细胞(HSC)受体介导的靶向脂质体(RGD SSL),观察包裹重组人干扰素α1b(IFNα1b)的长循环脂质体(SSL)对胆管结扎大鼠肝纤维化的治疗效果。方法实验大鼠随机分成4组假手术组、肝硬化模型组(BDL组)、IFN SSL治疗(BDL+IFN SSL)组、IFN配基SSL治疗(BDL+IFN RGD SSL)组,每组10只。构建包裹IFNα1b的SSL,通过聚乙二醇(PEG)将能与HSC特异性结合的配基[cyclo(RGD)]连接于脂质体的表面,观察对胆管结扎大鼠肝纤维化的治疗作用。检测各组大鼠血清肝功能、血清肝纤维化指标、肝组织羟脯氨酸含量、肝脏组织学的变化,运用RT PCR法检测肝脏Ⅰ型胶原的表达。分离HSC,用Western印迹检测α平滑肌肌动蛋白(αSMA)的表达。结果IFN RGD SSL治疗组大鼠肝纤维化程度均明显低于IFN SSL治疗组,肝功能指标、血清肝纤维化指标、肝羟脯氨酸含量和肝脏组织学改变较IFN SSL治疗组明显改善;肝脏Ⅰ型胶原mRNA和HSC的αSMA表达量明显下降。结论构建的受体介导的长循环脂质体对大鼠胆管结扎肝纤维化具有靶向性的治疗作用。
Objective To investigate the effect of long-circulating liposomes (SSL) encapsulating recombinant human interferon α1b (IFNα1b) on the growth of bile duct Effect of Ligation on Hepatic Fibrosis in Rats. Methods The experimental rats were randomly divided into four groups: sham operation group, BDL group, BDL + IFN SSL group and BDL + IFN RGD SSL group, 10 rats in each group . Construction of SSL encapsulating IFNα1b, coupling of ligand [cyclo (RGD)], which specifically binds to HSC, to the surface of liposomes by polyethylene glycol (PEG), and the therapeutic effect on liver fibrosis induced by bile duct ligation in rats . Serum liver function, serum hepatic fibrosis indexes, hydroxyproline content in liver tissue and liver histology were detected in each group. The expression of type Ⅰ collagen in liver was detected by RT-PCR. HSCs were isolated and the alpha smooth muscle actin (α SMA) expression was detected by Western blotting. Results The degree of hepatic fibrosis in IFN-RGD-treated group was significantly lower than that in IFN-treated group. The liver function, serum fibrosis index, liver hydroxyproline content and liver histological changes were significantly improved compared with IFN-SSL treatment group. ΑSMA expression of type Ⅰ collagen mRNA and HSC in liver decreased significantly. Conclusion The constructed receptor-mediated long-circulating liposomes have a targeted therapeutic effect on ligation of hepatic fibrosis in rats.