摘要
AIM: To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration.METHODS: Cirrhosis was induced in rats by administration of thioacetarnide. Untreated rats were used as controls. The control rats as well as the cirrhotic rats were subjected to 70% partial hepatectorny. At different time points after hepatectorny, the livers were collected and the levels of cytokines, growth factors and cell cycle proteins were analyzed.RESULTS: After hepatectomy, the cirrhotic remnant expressed significantly lower levels of cyclin D1, its kinase partner, cdk4, and cyclin E as compared to the controls up to 72 h post hepatectomy. Significantly lower levels of cyclin A and cdk2 were also observed while the cdk inhibitor, p27 was significantly higher. In addition, the cirrhotic group had lower IL-6 levels than the control group at all time points up to 72 h following resection.CONCLUSION: The data from our study shows that impaired liver regeneration in cirrhotic remnants is associated with low expression of cyclins and cdks. This might be the consequence of the low IL-6 levels in cirrhotic liver remnant which would in turn influence the actions of transcription factors that regulate genes involved in cell proliferation and metabolic homeostasis during the regeneration process.
瞄准:在与影响肝新生的因素的关系在对部分肝切除术的正常和硬变肝的回答检验差别。方法:肝硬化被 thioacetamide 的管理在老鼠导致。未经治疗的老鼠被用作控制。象肝脏硬化症的老鼠一样的控制老鼠受到 70% 部分肝切除术。在在肝切除术以后的不同时间点,肝被收集, cytokines,生长因素和房间周期蛋白质的层次被分析。结果:在肝切除术以后,当与直到 72 的控制相比 h 张贴肝切除术,肝脏硬化症的残余显著地表示了 cyclin D1,它的激酶搭挡, cdk4,和 cyclin E 的底层。当时,显著地, cyclin A 和 cdk2 的底层也被观察 cdk 禁止者, p27 显著地更高。另外,有的更低的 IL-6 比控制铺平的肝脏硬化症的组根本组织时间点直到 72 h 追随者切除术。结论:从我们的学习的数据证明在肝脏硬化症的残余的那个损害的肝新生与 cyclins 和 cdks 的低表示被联系。这可能是在将接着影响调整在新生过程期间涉及房间增长和新陈代谢的动态平衡的基因的抄写因素的行动的硬变肝残余的低 IL-6 层次的后果。
基金
Supported by a research grant from the National Medical Research Council,Singapore(awarded to T.M.C.Tan as PI and C.K.Leow as co-PI).