| Objective To measure the plasma levels of urokinase plasminogen activator(uPA), urokinase plasminogen activator receptor(uPAR) , plasminogen activator inhibitor-1(PAI-1) and the plasma levels of transforming growth factor-β 1 (TGF-β 1), and study the relationship between the plasma levels of uPA, PAI-1 and the plasma levels of TGF-β 1, the serum hyaluronic acid(HA), type Ⅲ procollagen (PCⅢ) in patients with different stages of liver cirrhosis following chronic hepatitis B. And observe the protein expressions of α-SMA, uPA, PAI-1, matrixmetallo-proteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the liver tissue, and the plasma levels of uPA, PAI-1 and TGF- β 1, and study on the relationships between the protein expressions of α -SMA and the protein expressions of PAI-1, TIMP-1 in patients with different grades of liver cirrhosis following chronic hepatitis B. To detect the protein expressions of α -SMA, uPA, PAI-1, type I and type Ⅲ collagen, TIMP-1, and TGF β 1, and the expressions of PAI-1 and TGF β 1mRNA in the cirrhotic liver tissue, and study the role and mechnism of urokinase on the hepatic fibrogenesis in rats.Method 1. 72 cases with liver cirrhosis of different stages were classifiedaccording to child-pugh's categories A, B, C, in which there were 23 cases in child A, 29 cases in child B, 20cases in child C. The plasma levels of uPA, uPAR, PAI-1 and the serum levels of HA, CIV were detected by ELISA. The serum PCIII concentration was determined by radioimmunoassay and the serum albumin(Alb), the serum total bilirubin(TB) , prothrombin time(PT) and prothrombin activity(PTA) by chemicalanalyser. 2. 37 cases with liver cirrhosis of different grades were classified according to HE and VG staining categories 0~4, in which there were 8 cases in grade 1, 9 cases in grade 2, 7 cases in grade 3? 13 cases in grade 4. The plasma levels of uPA , PAI-1 and TGF- P 1 and the serum levels of HA were detected by ELIS A. The protein expressions of a -SMA, uPA, PAI-1 and MMP-1, TIMP-1 in cirrhosis liver tissue were observed by immunohistochemistry. 3. Liver cirrhosis was induced in rats by complex pathogenic factors including subcutaneous injections of carbon tetrachloride, drinking alcohol and feeding cholesterol food. These animals were randomly devided into 4 groups: normal group(normal diet), uPA prevention group(complex pathogenic factors+uPA for 6 weeks), liver cirrhosis group(complex pathogenic factors for 6 or 8 weeks) and uPA treatment group(complex pathogenic factors+uPA for 7th and 8 th week). The animals were harvested on week 6, 8. The protein expressions of a -SMA, uPA, PAI-1, collagen type I and type III, and TIMP-1 in cirrhosis liver tissue were observed by immunohistochemistry, the expressions of PAI-1 and TGFP lmRNA in the cirrhotic liver tissue by quantitative reverse transcriptionploymerase chain reaction(RT-PCR). The serum levels of hyaluronic acid(HA) , alanine aminotransferase(ALT) , aspartate aminotransferase(AST) , bilirubin(TB), and the content of liver hydroxyproline(Hyp) were detected.Result 1. With the progression of hepatic fibrosis, the plasma levels of uPA, uPAR , PAI-1 and TGF- P 1 were all increased and the highest levels were in child C. The value of PAI-1/uPA was significantly decreased in childA, but increased in childB and childC. There was negative correlation between the plasma levels of uPA and the serum PClII(r=-0.4783, P<0.05) and positive correlation between the plasma levels of uPA and the plasma TGF- P l(r=0.4349, P <0.05) in childA. But, the plasma PAI-1 revealed a significant correlation with the serum HA(r=0.5471, PO.01) and there was positive correlation between the plasma levels of TGF- P 1 and the serum PCIII in child C(r=0.7860, PO.01). 2. During the progression of hepatic fibrosis, the plasma levels of uPA, PAI-1 and TGF-P 1 and the protein expression of a -SMA, uPA, PAI-1 and MMP-1, TIMP-1 in cirrhosis liver tissue were all increased. In grade 3 and 4, the plasma levels of TGF-P 1 and the protein expression of a -SMA, PAI-1 and TIMP-1 in cirrhosis liver tissue were significantly increased, but the protein expression of uPA and MMP-1 in cirrhosis liver tissue was not increased. In grade 4, there is positive correlation between the plasma TGF- P \ and the protein expression ofa -SMA (r=0.6474, P<0.05), and the protein expression of a -SMA revealed positive correlation with PAI-1 and TIMP-1 (r=0.5583, P<0.05; r=0.6679, P<0.05, respectively). 3. The liver cirrhosis was successfully induced by complex pathogenic factors in rat. In uPA prevention group, the serum ALT, AST, TB, the content of liver Hyp and the protein expression of a -SMA, PAI-1, TGF- P 1, TIMP-1, collagen typeI and type III, the expression of TGFP lmRNA in cirrhosis liver tissue were all decreased. But, the protein expression of a -SMA, PAI-1, TGF- P 1, TIMP-1, collagen type I and type III and the expressions of PAI-1 and TGF P lmRNA in cirrhosis liver...
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