Rudi J, Waldherr R, Raedsch R, Kommerell B
Department of Medicine, University of Heidelberg, Germany.
J Hepatol. 1995 Jan;22(1):43-9. doi: 10.1016/0168-8278(95)80258-4.
Expression of the proliferating cell nuclear antigen and Ki-67 antigen by hepatocytes was investigated in liver tissue specimens of 29 patients with primary biliary cirrhosis (stage I 13, stage II 6, stage III 5 and stage IV 5 patients) prior to treatment with ursodeoxycholic acid and of five control subjects using immunocytochemical methods. Proliferating cell nuclear antigen and Ki-67 expression were reevaluated in seven patients after 3 years of treatment with ursodeoxycholic acid. Proliferating cell nuclear antigen labelling indices were significantly higher in primary biliary cirrhosis (stage I, 6.4% to 32.4%, median, 10.9%; stage II, 9.6% to 21.6%, median 11.4%; stage III, 5.2% to 12.5%, median, 7.6%; stage IV, 3.8% to 8.9%, median, 5.6%) than in controls (0% to 0.5%, median, 0.1%; p < 0.005). Ki-67 antigen labelling counts were lower than proliferating cell nuclear antigen indices but elevated in all stages of primary biliary cirrhosis (stage I, 0.5% to 3.5%, median 2.0%; stage II, 1.8% to 3.6%, median 2.6%; stage III, 1.3% to 2.5%, median 1.9%; stage IV, 0.4% to 1.7%, median 1.0%) compared with controls (0% to 0.5%, median 0.3%; p < 0.005). After ursodeoxycholic acid treatment, mean proliferating cell nuclear antigen and Ki-67 labelling indices decreased from a median of 9.0% (range, 3.8% to 32.4%) to a median of 7.8% (range, 4.5% to 17.2%; p = 0.045) for proliferating cell nuclear antigen and from a median of 2.5% (range, 0.8% to 3.6%) to a median of 2.1% (range, 0.9% to 3.1%; p = 0.031) for Ki-67 antigen. It is concluded that hepatocyte proliferation is markedly increased in primary biliary cirrhosis, particularly in the early stages of the disease, and that ursodeoxycholic acid treatment reduces proliferative activity in primary biliary cirrhosis.
采用免疫细胞化学方法，对29例原发性胆汁性肝硬化患者（I期13例、II期6例、III期5例、IV期5例）在接受熊去氧胆酸治疗前的肝组织标本以及5例对照者的肝组织标本进行研究，检测肝细胞中增殖细胞核抗原（PCNA）和Ki-67抗原的表达情况。对7例接受熊去氧胆酸治疗3年的患者重新评估PCNA和Ki-67的表达。原发性胆汁性肝硬化患者的PCNA标记指数显著高于对照组（I期，6.4%至32.4%，中位数为10.9%；II期，9.6%至21.6%，中位数为11.4%；III期，5.2%至12.5%，中位数为7.6%；IV期，3.8%至8.9%，中位数为5.6%）（对照组为0%至0.5%，中位数为0.1%；p<0.005）。Ki-67抗原标记计数低于PCNA指数，但在原发性胆汁性肝硬化各阶段均升高（I期，0.5%至3.5%，中位数为2.0%；II期，1.8%至3.6%，中位数为2.6%；III期，1.3%至2.5%，中位数为1.9%；IV期，0.4%至1.7%，中位数为1.0%），与对照组相比（0%至0.5%，中位数为0.3%；p<0.005）。熊去氧胆酸治疗后，PCNA的平均标记指数从中位数9.0%（范围3.8%至32.4%）降至中位数7.8%（范围4.5%至17.2%；p = 0.045），Ki-67抗原的平均标记指数从中位数2.5%（范围0.8%至3.6%）降至中位数2.1%（范围0.9%至3.1%；p = 0.031）。结论是，原发性胆汁性肝硬化患者肝细胞增殖明显增加，尤其是在疾病早期，且熊去氧胆酸治疗可降低原发性胆汁性肝硬化的增殖活性。
