二乙基亚硝胺诱导小鼠肝癌的时钟基因表达变化

目的探讨在二乙基亚硝胺诱导的小鼠肝癌情况下时钟基因表达的变化。方法采用二乙基亚硝胺和CCL来诱导C57BL／6J小鼠肝癌，于16w后10：00处死小鼠取正常肝组织、癌旁组织和癌组织。提取总RNA并采用real—timeRT—PCR方法来检测肿瘤标志基因AFP，时钟基因Bmall、Dbp和Rev-Erba的表达。结果与正常组相比较，肿瘤标志基因AFP在肿瘤组织中明显上升；正常肝组织中Bmall表达较高，而Dbp和Rev—Erba表达较低，相比之下时钟基因Bmall在癌旁组织和癌组织中表达下降，降到正常组的1／3；时钟基因Dbp和Rev—Erba在癌旁组织和癌组织中表达则上升，达到正常组的2～4倍，癌旁组织与癌组织差异无统计学意义。结论小鼠正常肝组织时钟基因符合24h节律变化，在由二乙基亚硝胺诱导的肝癌情况下时钟基因表达发生紊乱。

DEN-Induced Hepatocellular Carcinoma is Associated with Aberrant Expression of Clock Gene in Mice

Objective To study expression of clock genes in diethylnitrosamine（DEN）-induced hepatoellular carcinoma in mice. Methods C57BL/6J mice were given DEN and CCl;for 16 weeks to induce hepatocellular carcinoma. At 16 weeks, normal livers,DEN-treated paracancerous and cancer tissues were collected to isolated total RNA. Expression of AFP, Bmall, Dbp and Rev-Erba genes were examined by real-time RT-PCR. Results DEN induced hepatocellular carcinoma after 16 weeks of administration. Compared with the normal group, the tumor marker gene AFP was significantly increased in tumor tissues. Normal livers at 10：00 had higher expression of Bmall and lower expression of Dbp and Rev-Erb~. In comparison,expression of clock gene Bmall was decreased in cancer and paracancerous tissues to 30% of normal group. Expression of clock genes Dbp and Rev-Erba were increased in cancer tissues and paracancerous tissues, by 2-4 fold over the normal group. There was no difference between paracancerous and cancer tissues. Conclusion DEN-induced hepatoma is associated with aberrant expression of clock genes in mice.