慢性乙型肝炎患者肝组织基质金属蛋白酶组织抑制物-1表达及其意义

Clinical significance of tissue inhibitor of metalloproteinases-1 in livers of patients with chronic hepatitis B

目的：分析慢性乙型肝炎患者血清和肝组织基质金属蛋白酶组织抑制物-1（TIMP-1）表达水平与肝纤维化分期的相关性。方法分别采用免疫组化法和双抗体夹心酶联免疫吸附法检测患者肝组织和血清 TIMP-1表达水平，分析两者相关性；对159例慢性乙型肝炎患者行肝活检病理学检查，以组织学活动指数（HAI）予以分级（G）和分期（S），分析慢性乙型肝炎患者血清 TIMP-1水平与 HAI 分级和纤维化分期的相关性。结果慢性乙型肝炎患者肝组织 TIMP-1表达水平与其血清水平呈显著性正相关（r=0.9521，P＜0.01）；不同肝纤维化分期（S1～S4）慢性乙型肝炎患者血清 TIMP-1水平差异显著（P＜0.05），且血清 TIMP-1水平与肝纤维化分期呈正相关（r=0.704， P＜0.01），但不同炎症分级的慢性乙型肝炎患者血清 TIMP-1水平差异无显著性。结论血清 TIMP-1水平可以较好地反应肝脏纤维化程度，且不受肝组织炎症分级的影响，有望被用于肝组织纤维化程度的临床无创评估。

Objective To evaluate the expression of tissue inhibitor of metalloproteinases-1 （TIMP-1） in livers of patients with chronic hepatitis B （CHB） and to explore the potential relationship between TIMP-1 level and hepatic fibrosis progression. Methods The tissue and serum levels of TIMP-1 were determined by immuno-histochemistry and double-antibody sandwich enzyme-linked immunoadsorbent assay,respectively,and their correla-tion was determined. One hundred and fifty-nine patients with CHB underwent liver biopsy and their liver histo-logical activity index （HAI） and fibrosis （S） were determined. The correlation between the serum TIMP-1 levels and HAI grading and staging was analyzed. Results The expression of TIMP-1 in liver tissues were positively correlated to serum TIMP-1 levels in CHB patients（r=0.9521,P〈0.01）;Serum TIMP-1 levels were significant dif-ferent among patients with different liver fibrosis stages （S1 to S4）（P〈0.05）,and a positive correlation between serum TIMP-1 level and hepatic fibrosis staging was found （r=0.704,P〈0.01）;However,there were no significant differences in serum TIMP-1 levels among patients with different liver inflammatory grades. Conclusions Serum TIMP-1 level is not affected by liver inflammatory grades and is promising in non-invasive clinical evaluation of liver fibrosis.