慢性乙型肝炎组织中肝前体细胞的免疫组化特征  

Immunohistochemical characterization of hepatic progenitor cells in chronic hepatitis B patients

作　　者：胡勇[1] 徐军[1] 周继 王健[1] 章太平[1] 余宏宇[3] 

机构地区：[1]解放军第105医院病理科,合肥230031 [2]合肥市瑶海区第二人民医院妇产科,合肥230011 [3]第二军医大学长征医院病理科,上海200003

出　　处：《临床与实验病理学杂志》2007年第5期574-577,共4页Chinese Journal of Clinical and Experimental Pathology

基　　金：解放军第105医院科研基金(No2006004-A)

摘　　要：目的研究肝前体细胞(hepatic progenitor cells,HPCs)、小管样反应、中间型肝细胞在慢性乙型肝炎组织中的分布特征和数量变化,以及与肝细胞再生之间的可能联系。方法对42例慢性乙型肝炎组织行常规病理HE染色,按炎症活动度(G)分为轻、中、重三度,免疫组织化学方法观察肝胆细胞标记(AFP、GST-π、CK7、CK19)和造血干细胞标记(c-kit、CD34)的表达,并以Ki-67标记增殖的肝细胞,用CK7/CK19作为标记物对符合定义的HPCs、中间型肝细胞进行计数,小管样反应程度的判定利用彩色病理图象分析系统。结果慢性乙型肝炎的早期阶段即存在HPCs的活化和小管样反应,其数量随着炎症活动度的增加而增加,均表达CK7、CK19、GST-π和AFP,肝细胞增殖指数在轻、中度肝炎中逐渐增加,重度肝炎、肝硬化患者增殖的肝细胞数下降,而中间型肝细胞数量显著增加。小管样反应面积百分比与HPCs数目正相关(r=0.739,P<0.05),中间型肝细胞数目与HPCs数目正相关(r=0.614,P<0.05)。结论慢性乙型肝炎中不仅有成熟肝细胞增殖,也存在肝前体细胞活化和分化,可能参与肝脏损伤后的再生修复。Purpose To investigate the distribution of hepatic progenitor cells （ HPCs）, ductular reactions, intermediate hepatocytes and proliferating hepatocytes in chronic hepatitis B patients,so as to study the correlation between HPCs activation and liver regeneration. Methods Light microscopy and immunohistochemical methods were used to observe the expression of hepatic/cholangiocellular differentiation markers （AFP, GST-π, CK7, CK19） and hematopoietic stem cell markers （CD34 and c-kit） in several kinds of cells obtained from 42 liver samples of chronic hepatitis B patients. The specimens were graded into three groups according to the histological activity. The number of proliferating hepatocytes was assessed by immunostaining for Ki-67, HPCs and intermediate hepatocytes counting were determined by CK7/CK19 immunostaining, and image analysis was performed to evaluate the extent of ductular reactions. Resuits HPCs and ductular reactions were present early in disease, and correlated with disease activity, which were shown to express CK7, CK19, GST-π and AFP. The number of proliferating hepatocytes increased in mild and moderate hepatitis, but decreased in severe hepatitis and liver cirrhosis, meanwhile the number of intermediate hepatocytes increased significantly. There were strong correlations between the number of HPCs with the number of intermediate hepatocytes （ r = 0. 614, P 〈 0. 05 ） and ductular reactions （ r = 0. 739,P 〈 0. 05）. Conclusions Our findings support the concept that HPCs activiation and their differentiation into hepatocytes or cholangiocytes is an important pathway for liver regeneration taking place in chronic hepatitis B.

关 键 词：慢性乙型肝炎 肝前体细胞 免疫组织化学 

分 类 号：R364.3[医药卫生—病理学] R512.62[医药卫生—基础医学]