【摘要】 目的探讨肝硬化患者血浆尿激酶型纤溶酶原激活物(uPA)、尿激酶型纤溶酶原激活物受体(uPAR)、纤溶酶原激活物抑制剂-1(PAI-1)变化及其意义。方法检查确诊的72例乙肝后肝硬化患者,依据Child-Pugh分级分为3级,其中A级23例,B级29例,C级20例。健康志愿献血者6例做为正常对照组。酶联免疫吸附法(ELISA)测定血浆uPA、uPAR、PAI-1的变化。同时检测血浆TGF-β1、透明质酸、Ⅲ型前胶原(PCⅢ)变化以及血浆白蛋白、胆红素、凝血酶原活动度改变。结果随着肝硬化的进展,血浆uPA、uPAR、PAI-1逐渐增加,血浆TGFβ1、血透明质酸、Ⅲ型前胶原也明显增加。Child C组患者血浆uPA、uPAR、PAI-1水平明显高于ChildA、ChildB组。Child A组PAI-1/uPA值下降,而Child B组、Child C组PAI-1/uPA又复升高。Child C组血浆uPA、uPAR、PAI-1水平与正常组、Child A组相比,差异显著。在Child A组,血浆uPA与PCⅢ呈负相关,与TGFβ1正相关;在Child C组血浆TGFβ1与血Ⅲ型胶原呈正相关,与HA呈正相关。结论血浆uPA、uPAR、PAI-1变化与肝硬化发生发展密切相关。肝硬化晚期,虽然血浆uPA、PAI-1增加,但总的效应表现为uPA相对不足,肝基质纤维降解受抑。适当增加uPA活性,抑制TGFβ1的早期激活,抑制肝硬化晚期PAI-1过度表达,可能有助于抑制HSC的激活、增加肝细胞外基质降解,从而有助于延缓肝硬化的发生发展。更多还原

【Abstract】 Objective To measure the plasma levels of urokinase plasminogen activator（uPA）,urokinase plasminogen activator receptor（uPAR）,and plasminogen activator inhibitor-1（PAI-1） and the plasma levels of transforming growth factor-β₁（TGF-β₁）,and study the relationship between plasma levels of uPA,PAI-1 and the plasma levels of TGF-β₁,the serum hyaluronic acid（HA）,procollagen type Ⅲ（PCⅢ） in patients with different stages of liver cirrhosis following chronic hepatitis B.Methods Seventy-two patients with liver cirrhosis of different stages（n=72） were classified according to Child-Pugh’s categories A,B and C,23 in Child-Pugh A,29 in Child-Pugh B and 20 in Child-Pugh C.Plasma levels of uPA,uPAR,PAI-1 and serum levels of HA were detected by enzyme-linked immunosorbent assay（ELISA）.Serum PCⅢ concentration was determined by radioimmunoassay and serum albumin（Alb）,total bilirubin（TB） and prothrombin activity（PTA） by chemical analyser.Results With the progression of hepatic fibrosis,the plasma levels of uPA,uPAR,PAI-1 and TGF-β₁ were significantly elevated in patients with liver cirrhosis compared with normal controls and the highest levels were in Child-Pugh C.The ratio of PAI-1 to uPA was significantly decreased in Child-Pugh A,but increased in Child-Pugh B and Child-Pugh C.There was negative correlation between plasma levels of uPA and serum PCⅢ（r=-0.478 3,P<0.05） and positive correlation between plasma levels of uPA and plasma TGF-β₁（r=0.434 9,P<0.05） in Child-Pugh A.Whereas,plasma PAI-1 revealed a significant correlation with the serum HA（r=0.547 1,P<0.01） and there was positive correlation between plasma levels of TGF-β₁ and serum PCⅢ（r=0.786 0,P<0.01） in Child-Pugh C.Conclusion In advanced liver cirrhosis,increased PAI-1 together with uPA and uPAR are associated with overall inhibition of matrix degradation.The plasma levels of uPA and PAI-1 are correlated with the progression of liver cirrhosis.The plasma levels of uPA,PAI-1 and TGF-β₁ play an important role in the progression of liver cirrhosis.Therefore,inhibiting the early activation of latent TGF-β₁ or increasing uPA and inhibiting PAI-1 overexpress may contribute to matrix degradation and retard the progression of liver cirrhosis.更多还原