KGF及KGFR共表达促进铁过载肝细胞增殖

The co-expression of KGF and KGFR promotes proliferation of hepatic cells in iron overload rat

目的铁过载可以促进肝细胞的增生导致纤维化,但其确切机制尚不清楚。本文通过喂食大鼠3%羰基铁3个月后行70%部分肝切除建立动物模型,通过不同时间点(0,12,24,36h)研究铁过载肝细胞增殖的过程中KGF和KGFR的表达。方法我们通过免疫组织化学方法和非放射性原位杂交方法分别检测了KGF和KGFR的蛋白及mRNA水平。结果在正常组,各时间段铁沉积均未检测到。实验组在0小时肝实质细胞和肝间质细胞中铁沉积显著并且随时间而减少(12-36h)。KGF蛋白在正常组12小时肝小叶中央静脉周围的肝实质和肝间质中的细胞质中有表达,36小时这种表达达到最强,但是实验组KGF的表达在24小时最为显著。KGFR的表达在正常组中0小时肝实质细胞中出现,并随时间增加而逐渐增强,到36小时达到高峰。实验组0小时只检测出少量KGFR阳性细胞,到24小时达到高峰随后逐渐减少。KGF和KGFR mRNA的表达在实验组中24小时肝实质细胞同时达到最高。结论 KGF和KGFR的共表达在铁过载肝细胞的增殖过程中促进了肝细胞的增殖。

Objective Iron overload promotes proliferation of hepatic cells leading to fibrosis, but its exact mecha- nism is unclear . The purpose to investigate the expression of KGF and KGFR in the rats with 3 ~ carbonyl iron for 3 months by 70~ partial hepatectomy through the different time points （0,12,24,36 h） . Methods KGF and KGFR protein and mRNA levels were detected by immunohistochemistry and non-radioactive in situ hybridization. Results I- ron deposition of each period is not detected in normal group. The iron deposition in the hepatocytes and stromal cells was detect significantly at 0 h,then decreased over time （12-36 h） in iron overload group. The expression of KGF was found in the hepatocytes and stromal ceils around the central vein of hepatic lobule in normal group at 12 h,this the ex- pression reached the peak at 36 h,whilethe peak appeared at 24 h in the iron overload group. The expression of KGFR appeared at 0 h in the hepatocytes in the normal group,increased over time,and reached peak at 36 h. We only detected a small amount of the KGFR positive cells,decreased gradually after reaching peak at 24 h. The expression of KGF and KGFR mRNA in the hepatocyte reached peak at the same time in iron overload group. Conclusion The co-expression of KGF and KGFR promoted proliferation of hepatic cells by 70~ partial hepatectomy in iron overload rat.