阿司匹林对大鼠肝癌组织PCNA及cyclin D1表达的影响

Effects of aspirin on PCNA and cyclin D1 expressions in diethylnitrosamine induced hepatic cancer of the rat

目的观察阿司匹林对二乙基亚硝胺诱导肝癌形成大鼠肝脏细胞增殖核抗原（proliferating nuclear antigen，PCNA）及细胞周期蛋白（cyclin D1）表达的影响，探讨阿司匹林在肝癌发生发展过程中的作用。方法应用二乙基亚硝胺诱导大鼠肝癌模型，预防组饲料中添加阿司匹林，两组分别于第8、12、16周时处死大鼠6只，用免疫组化检测肝脏PCNA及cyclin D1，观察不同时期肝脏PCNA及cyclin D1表达的变化及肝癌发生率。结果预防组大鼠肝硬化发生时间较晚，程度较轻，肝癌发生少，16周时对照组4／6只大鼠发生肝癌（P〈0．05）。PCNA及cyclin D1的表达明显低于对照组，阿司匹林对大鼠PCNA的抑制作用在12～16周时比较明显（F=5．696，F=11．057，均P〈0．05），对cyclin D1的抑制作用在16周时比较明显（F=11．944，P〈0．05）。结论阿司匹林能降低诱癌大鼠肝脏PCNA及cyclin D1表达，对实验性大鼠肝癌的形成有抑制作用。

Objective To observe the effects of aspirin on PCNA and cyclin D1 expressions in diethylnitrosamine （DEN） induced hepatic cancer of the rat. Methods Sprague-Dawley （ SD ） rats were randomly divided into DEN group and DEN plus aspirin group. Each group was further divided into 8,12, 16 week subgroups. The expressions of PCNA and cyclin D1 in hepatic tissue were examined with inmunohistochemistry. Results In DEN plus aspirin group cirrhosis was less severe and carcinoma developed later than that in DEN group. Hepatic carcinoma occurred in four rats out of six in DEN group at the 16th week （P 〈0. 05）. In DEN plus aspirin group PCNA and cyclin D1 expressions were significantly lower than those in DEN group（ P 〈 0. 05 ） , inhibiting effects on cyclin D1 expression was evidently great at 16th week （F = 11. 944 ,P 〈 0. 05 ） and inhibiting effect on PCNA was obvious from 12th to 16th week （F = 5. 696 and F = 11. 057, P 〈 0. 05 ）. Conclusion Aspirin downregulates the expressions of PCNA and cyclin D1 in hepatic tissues and inhibits the genesis and development of DEN induced hepatic cancer of the rats.