促凋亡蛋白Bid在肝癌发生过程中的作用

Influence of pro-apoptosis protein Bid on hepatocarcinogenesis

目的探讨促凋亡蛋白Bid在肝癌发生中的作用。方法应用基因毒性药物二乙基亚硝胺(diethylnitrosamine,DEN)制备小鼠实验性肝癌动物模型,通过阻断(Bid缺陷小鼠)或诱导(抗Fas抗体注射)肝细胞凋亡过程,观察肝癌发生中Bid蛋白的作用。结果1.在致癌剂DEN和凋亡诱导剂抗Fas抗体注射小鼠后8个月,在野生型小鼠肝脏内瘤结节外周BrdU标记指数显著高于Bid缺陷的小鼠(P=0·016);2.野生型动物与Bid缺陷型动物比较,肝内瘤结节的个数、面积以及肝脏受累比率二者差异具有显著性(P值分别为0·025、0·002和0·004)。结论Bid缺陷小鼠对DEN诱导的肝癌具有明显的抵抗作用,这一作用可能与Bid的促增殖作用有关。

Objective To investigate how pro-apoptosis proteins Bid influence the development and progres of experimental liver cancer. Methods Mouse model was established by injection of 15 μg/g body weight careinogen-diethylnitrosamine （DEN）, then blocked or induced cell apoptosis signal pathway by employing Bid knock-out mice （ko） or injecting anti-Fas antibody to detect the influence of Bid protein on the development and progression of hepatocarainogenesis. Results 1. There was a significant higher level BrdU labeling index outside tumorigenesis loci of wild type （wt） mice than that in knock out mice at 8 month after DEN exposure and anti-Fas antibody injection （ P =0.016）. 2.The average number and area of tumorigenesis loci or nodules and percentage of liver area affected in wt mice were found much more than those in knock out mice （ P = 0.025, P = 0.002 and P = 0.004, respectively）. Conclusion Bid knock out mice show an obvious resistant to hepatocarcinogenesis initiated by DEN exposure, which might be relevant to promote cell proliferation of Bid protein.