替吉奥对二乙基亚硝胺诱导大鼠肝癌及PCNA蛋白表达的影响  

Effects of tegafur gimeracil and oteracil porassium compound on diethylinitrosamine induced hepatocarcinoma and PCNA expression in rats

作　　者：冯芹 孙宝存 夏文凯 刘松燕 李欣 

机构地区：[1]鲁南制药集团股份有限公司新药药理中心,山东临沂273400

出　　处：《现代预防医学》2015年第6期1081-1085,共5页Modern Preventive Medicine

摘　　要：目的探讨替吉奥对二乙基亚硝胺(Diethylinitrosamine DEN)诱导大鼠原发性肝癌的作用,并探讨其机制。方法采用CCl4增敏、DEN诱导的方法制备大鼠肝癌模型,给药组给予替吉奥灌胃。观察大鼠体重、肝重、肝指数;测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)及谷胱甘肽转移酶(r-GT)水平;用苏木素-伊红(HE)染色处理肝脏组织切片,光镜观察病理学改变。免疫组化方法检测PCNA表达。结果模型组有3只动物死亡,替吉奥组动物没有死亡;模型组肝脏湿重及肝脏指数明显大于空白组,替吉奥组明显低于模型组;模型组所有动物均可见肝组织癌变,替吉奥组可见4只动物肝组织癌变,其余8只可见坏死后肝硬化(尚未发生癌变),癌变发生率明显低于模型组;造模动物血清ALT、AST、ALP、γ-GT升高明显,替吉奥明显降低血清ALT、AST、ALP、γ-GT水平。替吉奥组肝硬化及肝癌组织中PCNA蛋白的表达显著低于模型组。结论替吉奥对二乙基亚硝胺诱导的大鼠原发性肝癌有明显的抑制和延缓作用,部分机制可能通过抑制肝癌大鼠肝组织中PCNA蛋白的表达,抑制肝癌细胞过度增殖,从而阻止或延缓大鼠肝癌的发生和发展。Objective The aim of this study was to evaluate the effects and mechanisms of tegafur gimeracil and oteracil porassium compound on CCl4 and diethylinitrosamine induced hepatocarcinoma in rats. Methods The models of hepatocarcinoma were induced by CCl4 and diethylinitrosamine. Tegafur gimeracil and oteracil porassium compound were orally given to the drug administration group. Changes of body weight, liver weight, and liver indexes were measured. The serum activities of ALT, AST,ALP and γ-GT were determined. Liver tissue sections were examined under microscope. Immunohistochemistry was employed to detect proliferating cell nuclear antigen（PCNA）. Results Three rats were dead in the model group, while no rats were dead in the drug administration group. Tegafur gimeracil and oteracil porassium compound markedly decreased liver weight and liver indexes.In the model group, the cancerization of liver tissues appeared in all rats. In the drug administration group, four rats showed cancerization, and eight showed postnecrotic cirrhosis（no cancerization yet）. The occurring rate of hepatocarcinoma for the drug administration group was significantly lower than that for the model group. The levels of ALT, AST, ALP and γ-GT in the drug administration group were significantly lower than those in the model group. The expression of PCNA protein in the drug administration group was significantly lower than that in the model group. Conclusion Tegafur gimeracil and oteracil porassium compound can inhibit the proliferation of hepatocytes induced by DEN, then can slow down the development of hepatocarcinoma.

关 键 词：二乙基亚硝胺 增殖细胞核抗原 原发性肝癌 替吉奥 

分 类 号：R319[医药卫生—基础医学]