乙肝病毒和黄曲霉毒素B_1诱发树鼠句肝癌的病理变化

Serial pathologic changes in liver of tree shrew during hepatocarcinogenesis induced by hepatitis B virus and aflatoxin B_1

目的 :对人乙型肝炎病毒 (HBV)和 (或 )黄曲霉毒素B1(AFB1)引起的树鼠句肝脏病变进行动态比较观察。方法 :成年树鼠句按不同处理分为A(HBV +AFB1)、B(HBV)、C(AFB1)、D(空白对照 ) 4组。全部动物定期肝活检 ,并于 16 0周结束实验时处死所有存活者。各次活检及尸检肝组织均作常规病理组织学检查 ,部分同时作HBsAg及HBxAg免疫组织化学、HBV DNA原位杂交 ,以及PAS、网状纤维染色等检查。结果 :肝组织的炎症及肝细胞增生性改变以A组最明显 ,B组病变发生虽早但发展较慢 ,C组病变发生较迟 ,但发展较快。肝细胞癌 (HCC)仅见于A、C组 ,其发生率及平均发生时间在A、C组分别为 6 7% (14/2 1)和 30 % (3/ 10 ) ,以及 12 0周和 15 3周 (P <0 0 1)。B组虽无HCC发生但可见较大增生或结节形成。D组无明显增生灶或结节。HBV感染标志在整个实验过程中可在A、B组大多数动物的肝组织中检出 ,其阳性检出率波动于 5 0 %～ 90 %。结论 :树鼠句模型适用于对人类肝炎、肝癌等病变的研究。HBV和AFB1具有协同致肝癌作用。

Purpose To serially observe and compare the pathologic changes in tree shrews liver during hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B 1 (AFB 1). Methods Adult tree shrews were divided into four groups. Group A:HBV infection and AFB 1 feeding; Group B:HBV infection only; Group C:AFB 1 feeding only; Group D:neither HBV nor AFB 1 treatment. All the animals in each group were regularly biopsied on liver. The experiment ended at 160th week when all the survivals were autopsied. All the liver samples from biopsies and autopsy were examined histopathologically by HE staining. Some samples were simultaneously stained for HBsAg/HBxAg by immunohistochemistry, HBV DNA by in situ hybridization, PAS and reticular fiber staining were also performed. Results Inflammatory changes and liver cell proliferation were the most obvious in group A; these kinds of changes appeared relatively earlier but progressed slower in group B than in group C. HCC occurred only in group A and group C. The tumor incidence and the average time for HCC appearing in these two groups were 67% and 30%,120 weeks and 150 weeks( P <0 01) respectively. Even though no true HCC occurred in group B, there were some large proliferation nodules. No proliferation foci/nodules occurred in group D. The markers of HBV infection appeared frequently in group A and group B during the whole experiment, with the positive rate of 50%～90%. Conclusion The tree shrews model is applicable for the research on human hepatitis B and HCC.