慢性乙型肝炎血清MMP-1和TIMP-1与肝脏炎症及肝纤维化的相关性

Correlation between serum MMP-1,TIMP-1 and liver pathology in patients with chronic hepatitis B

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 of serum matrixmetalloproteinase-1 （ MMP-1 ）, tissue inhibitor of metalloprotienase-1 （ TIMP-1 ） with the severity of liver fibrosis and inflammation. To look for the index sign of serology of the new judgment of hepatic fibrosis degree. Methods Liver pathology was performed in 64 patients with chronic hepatitis B （CHB） ; hepatic histological findings were diagnosed by liver inflammation grades （ G ） and fibrosis stages （ S ） ; serum levels of MMP-1 ,TIMP-1 were detected by sandwich enzyme-linked immunosorbent assay （ELISA） ;serum levels of hyaluronidase（ HA ）, Laminin（ LN）, collagen-Ⅳ （ C-Ⅳ ） and procollgen tpye Ⅲ peptide（ PⅢNP） were detected by radioimmunoassay. Results With the development of liver inflammation grades and fibrosis stages,the serum levels of MMP-1 gradually reduced,but the serum levels of TIMP-1 increased gradually;besides, there were no significant differences between the G1 and G2 ,the S1 and S2 ,the rest groups comparison had significant differences;serum TIMP-1 was correlated positively with the fibrosis stages（ P =0. 003 ） and inflammation grades（ P = 0. 005 ）. However, serum MMP-1 was correlated negatively with the fibrosis stages （ P = 0. 004 ） and inflammation grades （ P = 0. 007 ） ; serum MMP-1, TIMP-1 had good correlation with serum HA,PⅢNP. Conclusion Serum MMP-1 and TIMP-1 levels can be used as fibrosis markers.