中文摘要：

目的：探讨骨形态发生蛋白-4（BMP-4）对大鼠肝干细胞系WB-F344的增殖及分化的影响。方法：采用50 ng/mL的基因重组BMP-4作用于WB-F344细胞,以BMP-4拮抗剂Noggin（200 ng/mL）阻断BMP-4的作用为对照。在实验不同时间点,通过四甲基偶氮唑盐（MTT）比色法检测BMP-4对WB-F344增殖的影响,透射电镜下观察细胞的超微结构特征,RT-PCR检测各试验组中WB-F344细胞可能分化表型特异性分子标志物的mRNA表达。结果：细胞增殖实验显示：在不同作用时间点,BMP-4干预组的细胞吸光值均高于Noggin处理组和空白对照组。透射电镜下可观察到BMP-4干预后的WB-F344细胞具有分化良好的上皮细胞的超微结构特征。RT-PCR显示BMP-4诱导WB-F344分化后,肝干细胞的肝细胞特异性分子标志物的mRNA显著表达。结论：BMP-4可促进肝干细胞WB-F344的增殖,并诱导其向肝细胞定向分化。

英文摘要：

Objective To determine the regulation effect of bone morphogenetic protein-4（BMP-4） on the proliferation and differentiation of rat hepatic precursor cells.Methods We used Noggin（200 ng/mL） as the function blocking control of BMP-4,and the hepatic precursor cells of WB-F344 were treated with recombinant BMP-4 at 50 ng/mL at different time points.The proliferation of WB-F344 cells were tested by methyl thiazolyl tetrazolium（MTT） colorimetric assay.The ultrastructural characters of differentiated WB-F344 cells regulated by BMP-4 were observed under a transmission electron microscope.RT-PCR was used to examine mRNA expression of specific molecular markers for different cellular phenotypes potentially differentiated from the WB-F344 cells.Results At different time points,the absorbance values in the BMP-4 treatment groups were higher than those in the control groups of Noggin and blank treatment（P0.01）.The WB-F344 cells treated with BMP-4 exhibited typical ultrastructural characters of well-differentiated epithelial cells.The hepatocyte mRNA markers were more significantly promoted in the differentiated WB-F344 cells in the BMP-4 treatment group than those in the other 2 control groups.Conclusion BMP-4 can promote the proliferation and directional differentiation towards hepatocytes of rat hepatic precursor cells of WB-F344.