A study of the effect of hormone and growth factor on liver regeneration

为阐明肝再生的机制，我们观察了肝再生过程中原癌基因表达的变化，本实验观察了大鼠肝部分切除术后不同时间再生肝组织中c-myc、fos、Ha-ras、erbA基因、雌激素受体（ER）和维生素D受体（VDR）的表达。c-myc mRNA在3 h达到最高水平3倍，8h内降至基础水平。在肝再生过程中，c-Ha-ras表达水平在12 h时升高至2倍，而c-erbA mRNA表达无明显增加。另外，原位杂交方法也显示c-myc mRNA在3 h时出现在肝细胞胞质中，myc蛋白在6 h时出现在肝细胞核中，近年来，研究发现癌基因产物与激素受体、生长因子及其受体密切相关，因此我们对分别与erbA和myc基因相关的ER和VD-R进行了研究。ER在3 h迅速下降至基础水平的1/2倍，尽管erbA无变化。术前未检测到的VD-R在PH后6 h开始检测到并达到高峰，c-myc和VD-R表达变化的平行性提示c-myc和VD-R在肝细胞中的表达密切相关。为了研究雌激素是否能够促进肝再生，我们在PH前用雌二醇处理大鼠。然而，我们不能获得结果，表明雌激素在7天内显著增加肝体积，尽管与未处理的大鼠相比，ER长时间保持在低水平。不幸的是，活性维生素D和生长因子的作用的评价，特别是表皮生长因子对肝再生的影响还有待研究。

In an attempt to elucidate the mechanisms of liver regeneration, the changes of protooncogene expression (c-myc, fos, Ha-ras, erbA), estrogen receptor (ER) and vitamin D receptor (VDR) were investigated in rat regenerating liver at different times after partial hepatectomy(PH).Levels of c-fos mRNA elevated quickly to 2.5-fold within 45 min after PH and also decreased rapidly by 1h, c-myc mRNA reached maximal level of 3 fold at 3h and fell to basal level within 8h. Levels of c-Ha-ras elevated to 2-fold at 12h, but c-erbA mRNA did not demonstrate any significant increase during liver regeneration. Alternatively, c-myc mRNA were also demonstrated in hepatocyte cytoplasm by in situ hybridization method at 3h and myc protein product in hepatocyte nuclei at 6th immunohistochemically.Recently, a close relationship between oncogene products and hormone receptor or growth factor or its receptor were indicated, therefore we investigated ER and VD-R which have some association with erbA and myc genes respectively. ER rapidly declined to 1/2-fold of basal level at 3h, despite no change in erbA. VD-R which was not detected in preoperative liver, became detectable and reached a peak at 6h after PH.Hence, the parallelism in change of c-myc and VD-R expression suggested that there is a close relationship between c-myc and VD-R expression in hepatocyte. To investigate whether estrogens are able to promote liver regeneration, we treated rat with estradiol before PH. However, we were unable to obtain a result which indicated that estrogen raises significantly liver volume in 7 days, although ER stayed at a low level for long duration compared to non treated rats.Unfortunately the evaluation of the effect of active vitamin D and growth factor, especially epidermal growth factor on liver regeneration remains to be done.