重型乙型肝炎患者肝组织中人纤维介素基因的表达及意义

Expression of human fibroleukin gene acute on chronic hepatitis B and its clinical significance

目的 研究人纤维介素基因 (hfgl2凝血酶原酶 /hfgl2 )在重型乙型肝炎患者肝组织内蛋白及mRNA水平的特异性表达 ,hfgl2表达的细胞类型及其与纤维蛋白沉积、微血栓及肝细胞坏死形成之间的关系。方法 采用免疫组化法研究了 2 3例重型乙型肝炎、13例慢性乙型肝炎、14例乙型肝炎肝硬化患者的肝组织及重型乙型肝炎患者的肝外组织中hfgl2的表达 ,同时制备hfgl2cDNA探针并对上述组织进行原位杂交以了解其在mRNA水平的表达。对枯否氏细胞表面标志CD6 8、纤维蛋白进行了检测。进一步对在重型肝炎肝组织中hfgl2凝血酶原阳性标本进行了hfgl2凝血酶原酶和纤维蛋白双染色。结果 2 1例重型乙型肝炎患者肝组织中可见hfgl2表达 ,而在慢性乙型肝炎、乙型肝炎肝硬化患者的肝组织、重型乙型肝炎肝炎的肝外组织均无hfgl2表达。重型乙型肝炎肝组织枯否氏细胞明显增生活化 ,主要分布于炎性坏死区 ,表达hfgl2之细胞主要为活化枯否氏细胞和血管内皮细胞 ,邻近组织发现有纤维蛋白的沉积和微血栓的形成。结论 hfgl2在重型乙型肝炎肝组织活化枯否氏细胞中的异常表达 ,激活凝血酶原 ,启动局部的凝血过程 ,导致纤维蛋白的沉积、微血栓的形成、微循环障碍和局部炎性反应 ,并最终引发肝细胞大量坏死 。

Objective To investigate the mRNA and protein expressions of human fibroleukin gene (hfg12) in acute on chronic (AOC) hepatitis B and its clinical significance. Methods Liver tissues were obtained from 23 patients with AOC hepatitis B, 13 patients with chronic hepatitis, and 14 patients with cirrhosis to be examined histologically. Immunohistochemisrty and in situ hybridization were used to detect the mRNA and protein expressions of hfg12 in the liver tissues. Double staining was used to the hfg12 positive samples to examine both the hfg12 and fibrin. Four specimens of liver tissue from normal donors were used as controls. Results Immumohistochemistry showed that hfg12 was expressed in the liver tissues of 21 out of the 23 patients with AOC hepatitis B (91.30%) and only one out of the 13 patients with chronic hepatitis (7.69%). In situ hybridization showed that hfg12 was expressed in the liver tissues of 13 out of he 23 patients with AOC hepatitis B and in none of the 27 patients with chronic hepatitis or cirrhosis. In patients with AOC hepatitis Kupffer's cell, CD68 positive, was numerous and big, mainly distributed in the necrosis areas. It was identified as the same of hfg12-expressing cells. Conclusion High expression of hfg12 is one of the molecular mechanisms of necrosis of liver cells in AOC hepatitis.