Research Of The Correlation About The Expression Of MMP-1 And TIMP-1 In Hepatic Fibrosis Tissues And Concentrations Of MMP-1 And TIMP-1 In Peripheral Blood Associated With Liver Pathological Grade

Objective:To approach the expression of Matrix metalloproteina- se-1(MMP-1) and Tissue inhibitors of metalloproteinase-1(TIMP-1) in the hepatic tissue from patients who suffered chronic hepatitis B or cirrhosis after Hepatitis B and the concentration of MMP-1 and TIMP-1 in peripheral venous blood from the patients above, to analyse the correlation about the two things above separately associated with the liver inflammatory activity grade and fibrosis staging in the aspect of clinic patholog, in order to provide theoretical basis for the thing that is to find new serum index which can judge the degree of hepatic fibrosis to take the place of the invasive liver puncture biopsy.Methods: To Choose 28 cases of patients who suffered chronic hepatitis B or cirrhosis after hepatitis B and were treated in hospital or in out-patient clinic in The First Affiliated Hospital of Guangxi Medical University from October 2007 to May 2008 .All patients were punctured out a bit of liver tissue by liver puncture biopsy for pathological examination,the latter can judge liver inflammatory activity grade (G) and fibrosis staging (S), simultaneously collecting the serum of all the patients above, and collecting 47 cases of serum from healthy examination persons in the same period as control serum..To determine positive rate and degree of staining about the expression of MMP-1 and TIMP-1 in liver cells of liver fibrosis tissue by two-step method which is a immunohistochemical method,and determine the concentration of MMP-1 and TIMP-1 in serum by using double-antibody sandwich enzyme-linked immunosorbent assay.Results:①The expression of TIMP-1 protein in the liver tissues from paients who suffered chronic hepatitis B or cirrhosis after Hepatitis B was positively correlated with liver fibrosis staging (r = 0.386, P = 0.042); with the heavier degree of liver fibrosis, The expression of MMP-1 protein in the liver tissues above showed no significant correlation with liver fibrosis staging (P> 0.05); the Statistics about the expression ratio of MMP-1 and TIMP-1 also showed no significant correlation with liver fibrosis staging (r =- 0.366, P = 0.056).②With the heavier degree of liver fibrosis, the concentration of MMP-1 in serum gradually decreased, while the concentration of TIMP-1 in serum gradually increased.Comparing of the normal group and each group of liver fibrosis staging, the results about the determination of MMP-1 and TIMP-1 indicate that all of the Comparisons between the each pair of next-to-next groups had no significant difference, but the Comparisons between the each pair of nonadjacent groups showed that only a few reslults indicated no significant difference. The Statistics of the comparisons about the concentration ratio of MMP-1 and TIMP-1 between each two groups were irregular.③With liver inflammation activity increasing, the concentration of MMP-1 in serum decreased, while the concentration of TIMP-1 in serum gradually increased. Comparing of the normal group and each group of inflammation grade, the results about the determination of MMP-1 and TIMP-1 indicated that all of the Comparisons between the each pair of next-to-next groups had no significant difference, but the Comparisons between the each pair of nonadjacent groups were all significantly different (α= 0.05); The results of the comparisons about the concentration ratio of MMP-1 and TIMP-1 between each two groups were irregular.④the concentrations of TIMP-1 in serum were positively correlated with the degree of liver fibrosis staging (r = 0.646, P = 0.000), and were positively correlated with liver inflammation activity grade (r = 0.622, P = 0.000); the concentrations of MMP-1 in serum and were highly negatively correlated with the degree of liver fibrosis staging (r =- 0.83, P = 0.000), and were highly negatively correlated with liver inflammation activity grade (r =- 0.821, P = 0.000); the concentration ratio of MMP-1 and TIMP-1 in serum were highly negatively correlated with the degree of liver fibrosis staging (r =- 0.776, P = 0.000), and were highly negatively correlated with liver inflammation activity grade (r =- 0.757, P = 0.000)⑤the concentrations of MMP-1 and TIMP-1 in serum had no significant correlation with the expression of the MMP-1 and TIMP-1 in liver tissues respectively.(P> 0.05).Conclusions:(1) Determination of TIMP-1 in liver tissues of liver fibrosis is a useful index, and has important significance for reflecting the degree of liver fibrosis. Determination of MMP-1 in liver fibrosis can not be regarded as a index of hepatic fibrosis judgment. The index of the expression ratio of MMP-1 and TIMP-1 in liver tissues can not be used for diagnosing hepatic fibrosis and judging the liver fibrosis staging.(2)The concentration of MMP-1 and TIMP-1 and the concentration ratio of MMP-1 and TIMP-1 in serum all can not well discriminate each staging of liver fibrosis and each grade of liver inflammation activity, and are not suitable to dynamicly judge the degree of liver fibrosis and liver inflammation activity grade.However, all of the three indexes are well correlated with liver fibrosis staging and liver inflammation activity grade,and can indirectly reflect liver damage degree of chronic active hepatitis,and can offer important reference for diagnosis and prognosis judgement.(3) The concentration of MMP-1 in serum may have higher correlation with hepatic fibrosis than TIMP-1. The concentrations of MMP-1 and TIMP-1 in serum respectively have the the correlativity with liver fibrosis staging close to with liver inflammation activity grade.(4) The concentrations of MMP-1 and TIMP-1 in serum respectively have no correlation with the expression of MMP-1 and TIMP-1 in liver tissues.