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目的观察慢性乙型肝炎患者血清基质金属蛋白酶-1(MMP-1)及基质金属蛋白酶组织抑制因子-1(TIMP-1)与肝脏炎症活动度及纤维化程度的相关性。方法选择2005年6月至2006年10月广州市第八人民医院收治的慢性乙型肝炎患者64例,均行肝穿刺活检病理组织检查并进行肝脏炎症活动度分级(G)及纤维化程度分期(S)。用双抗体夹芯酶联免疫吸附试验检测血清MMP-1及TIMP-1,用放射免疫法检测血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原N端肽(PⅢNP)、Ⅳ型胶原(C-Ⅳ)。结果随着肝脏炎症活动度及纤维化程度加重,血清MMP-1逐渐降低,而TIMP-1逐渐升高,除G1期与G2期患者比较,S1期与S2期患者比较差异无显著性意义外,其余各级别患者之间两两比较差异均有显著性意义(P<0.05或P<0.01)。血清TIMP-1与肝脏纤维化程度分期呈正相关(P=0.003),与肝脏炎症活动度分级呈正相关(P=0.005);血清MMP-1与肝脏纤维化程度分期呈负相关(P=0.004),与肝脏炎症活动度分级呈负相关(P=0.007),且血清MMP-1和TIMP-1与HA、PⅢNP具有良好相关性。结论血清TIMP-1和MMP-1对评估肝纤维化程度有一定的参考价值。
Objective To investigate the relationship between serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and liver inflammation and fibrosis in chronic hepatitis B patients. Methods Sixty-four patients with chronic hepatitis B who were admitted to the Eighth People’s Hospital of Guangzhou from June 2005 to October 2006 were examined by liver biopsy and pathological grade of liver inflammation (G) and stage of fibrosis (S). Serum levels of MMP-1 and TIMP-1 were detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the levels of serum hyaluronic acid (HA), laminin (LN), type Ⅲ procollagen N-terminal peptide ), Type Ⅳ collagen (C-Ⅳ). Results With the aggravation of hepatic inflammatory activity and fibrosis, serum MMP-1 decreased gradually and TIMP-1 gradually increased. There was no significant difference between S1 and S2 patients except G1 and G2 (P <0.05 or P <0.01). There was significant difference between the other levels of patients in any pairwise comparison (P <0.05 or P <0.01). The serum level of TIMP-1 was positively correlated with the stage of liver fibrosis (P = 0.003), and positively correlated with the grade of liver inflammation (P = 0.005). The serum level of MMP-1 was negatively correlated with the stage of hepatic fibrosis (P = 0.004) (P = 0.007), and serum MMP-1 and TIMP-1 had a good correlation with HA and PⅢNP. Conclusions The serum levels of TIMP-1 and MMP-1 have some reference value in evaluating the degree of liver fibrosis.