纤溶酶原激活物抑制物在纤维化肝组织中的表达及其血浆活性检测

Expression and plasma activity of plasminogen activator inhibitor-1 in fibrotic liver tissues

目的研究和探讨纤溶酶原激活物抑制物（ｐｌａｓｍｉｎｏｇｅｎ ａｃｔｉｖａｔｏｒ ｉｎｈｉｂｉｔｏｒ－１， ＰＡＩ－１）在人肝纤维化组织中分布、作用及血浆中活性水平的变化。方法采用原位杂交和免疫组织化学方法检测正常人，慢性乙型肝炎及肝硬化患者肝组织中ＰＡＩ－１ｍＲＮＡ和蛋白表达，并对蛋白表达的半定量结果与肝纤维化程度进行对比分析。同时采用发色底物法检测血浆中ＰＡＩ－１活性。结果随肝纤维化程度的加重，血浆ＰＡＩ－１活性下降；ＰＡＩ－１蛋白表达着色积分增加。无论ＰＡＩ－１ｍＲＮＡ还是蛋白表达均于血管腔面及肝纤维化活跃的汇管区、肝细胞变性坏死处、纤维间隔和毗邻以上部位的肝细胞浆见明显的阳性染色。结论肝脏中ＰＡＩ－１的细胞学来源除了间质细胞，还有肝实质细胞；亦提示ＰＡＩ－１与肝纤维化密切相关。

Objective To study plasminogen activator inhibitor-1 (PAI-1) gene expression and protein synthesis in fibrotic liver tissues and plasma activity levels. Methods Plasma PAI-1 activity was detected by chromogenic activity assay kit. The messenger RNA (mRNA) of PAI-1 and PAI-1 protein was detected on serial biopsied liver specimens of normal, HBV-related chronic hepatitis and cirrhosis by in situ hybridization and immunohistochemistry. The semi- quantitative results of the protein expression to immunohistochemistry staining were analysed in contrast with the stage of hepatic fibrosis. Results The plasma PAI-1 activity levels decreased with the progression of hepatic fibrosis. PAI-1 mRNA and protein were expressed in the extracellular matria deposition of the portal areas, focal necrotic areas, fibrous sepia and hepatocytes as well as the hepatocellular cytoplasm adjacent to the areas described above. Conclusion Localization of PAI-1 is not only in interstitial cells but also hepatocytes, suggesting an intense relationship between PAI-1 and hepatic fibrosis.