大鼠胰腺癌和非癌胰腺组织Skp2和p27表达研究

Expressions of Skp2 and p27 in Pancreatic Cancer and Non-cancerous Pancreatic Tissues of SD Rats

目的 建立大鼠胰腺癌模型，研究大鼠胰腺癌和非癌胰腺组织中Skp2和p27表达及其意义。方法 应用二甲基苯并蒽（DMBA）置人大鼠胰实质内（A组）及设立曲古霉素（TSA）干预组（B组），3～5个月内处死观察胰腺癌发生情况，应用SP免疫组化法研究胰腺癌和非癌胰腺组织中Skp2和p27表达。结果 3～5个月内A组发癌率为48．7％（18／37），B组为33．3％（12／36），A组和B组各1例纤维肉瘤外，余均为胰腺导管癌；A组肿块最大径大于B组（P〈0．05）；非癌胰腺组织中A组导管上皮中至重度不典型增生者（52．6％）高于B组（33．3％），但差异无显著性（P〉0．05）；C组胰腺和A或B组鼠胰腺外主要脏器均无明显病变。A组和／或B组胰腺导管癌Skp2表达阳性率均明显高于A组和／或B组非癌胰腺组织（P〈0．05）；但胰腺导管癌p27表达阳性率明显低于非癌胰腺组织（P〈0．01）；Skp2阳性和p27阴性的非胰腺组织导管上皮均呈中至重度不典型增生；C组胰腺导管上皮Skp2均阴性表达和p27均阳性表达。结论 DMBA置入胰实质内可在短期获得较高的SD鼠胰腺癌发生率，TSA能抑制胰腺癌发生和生长。Skp2和p27表达水平与SD鼠胰腺癌发生发展有密切关系。

Objective To establish a pancreatic cancer model of SD rats, and to study the expressions of Skp2 and p27 in pancreatic cancer and non - cancerous pancreatic tissues of SD rats. Methods The membrane and panrenchyma of rat＇s pancreas was opened to implant 9mg DMBA. The rats in the intervering group （group B） were treated with 1ml trichostatin （TSA） saline solution （1ml/L） intraperitoneally every week. The pancreas and other organs of rats sacrificed within 3 - 5 months were inspected and the specimens were routinely paraffin - embedded. The expressions of Skp2 and p27 were analyzed by SP immunohistochemistry. Results The prevalence of pancreatic cancer in the model group （group A） within the first 3--5 months was 48.7% （18/37）, including 17 pancreatic ductal adenocarcinoma and 1 fibrosarcoma. The prevalence of pancreatic cancer in the group B was 33.3 % （12/36）, including 11 pancreatic ductal adenocarcinoma and 1 fibrosarcoma. The maximal diameters of tumor mass of group A was significantly higher than that of group B （P〈 0.05）. The prevalence of the middle or severely - atypical hyperplasia of ductal epithelia in group A was higher than that in group B （52.6 % vs 33.3 %, but P 〉0.05）. The pancreas of group C and other main organs of groups A and B did not show pathological changes. The positive rate of Skp2 was significantly higher in pancreatic ductal adenocarcinoma tissues than that in the non - cancerous pancreatic tissues of rats in groups A and/or B. But the positive rates of p27 showed the opposite results. The positive cases of Skp2 and the negative cases of p27 in non - cancerous pancreatic tissues showed rfiiddle - or serverly- atypical hyperplasia of ductal epithelia. The pancreatic ductal epithelia of group C showed negative expression of Skp2 and positive expression of p27. Conclusion DMBA directly implanted into the parenchyma of pancreas could induce an ideal rat pancreatic cancer model with high incidence in an acute course. TSA shows an inhibitive effect on the carcinogenesis and growth of rat pancreatic cancer. The expression of Skp2 and p27 have close relationship with the carcinogenesis and progression of rat pancreatic cancer.