Comprehensive analyses of liver regeneration-and atrophy-related genes in rat model of liver transplantation using size-mismatch graft

半肝门静脉栓塞（PVE）同时引起栓塞肝叶萎缩和非栓塞肝叶代偿性肥大。本研究的目的是评估PVE后这些肝叶中生长刺激和抑制因子的参与。从10例PVE后2 ~ 3周行肝切除术的患者的栓塞和非栓塞肝叶中获得肝脏标本。用Ki-67和Tdt介导的dUTP-生物素缺口末端标记法检测细胞增殖和凋亡。PVE可诱导栓塞侧肝细胞凋亡，而非栓塞侧肝细胞增殖。未栓塞肝叶的肝细胞中TGF-α表达显著增加，而栓塞肝叶中TGF-α也过度表达，尽管是中度表达。相比之下，栓塞叶肝细胞中的TGF-β表达显著增加，并且TGF-β表达也在非栓塞叶中增加，尽管程度较小。PVE后未栓塞肺叶和栓塞肺叶的体积变化程度与TGF-α和TGF-β在这些肺叶中的表达比例相关（r=0.886，p<0.0001）。总之，这些发现表明TGF-α和TGF-β表达增加与肝细胞增殖和凋亡有关，两种因素的平衡可能导致在该模型中同时观察到的肝萎缩和肥大。

Hemihepatic portal vein embolization (PVE) concomitantly induces atrophy in embolized and compensatory hypertrophy in nonembolized hepatic lobes. The aim of the present study was to evaluate the involvement of growth stimulatory and inhibitory factors in these hepatic lobes after PVE.Liver specimens from the embolized and nonembolized lobes of 10 patients who had undergone hepatectomies 2 to 3 weeks after undergoing PVE were obtained. Proliferation and apoptosis were examined immunohistochemically using Ki-67 and the Tdt-mediated dUTP-biotin nick end labeling method. The expression of transforming growth factor-α (TGF-α) and transforming growth factor-β (TGF-β) was also examined by immunohistochemical staining.PVE induced hepatocyte apoptosis in the embolized lobe and hepatocyte proliferation in the nonembolized lobe. TGF-α expression in the hepatocytes of the nonembolized lobe was markedly increased, while TGF-α was also overexpressed, albeit moderately, in the embolized lobe. In contrast, TGF-β expression in the hepatocytes of the embolized lobe was significantly increased, and TGF-β expression was also increased, although to a lesser extent, in the nonembolized lobe. The degree of volume changes of the nonembolized lobe and the embolized lobe after PVE was statistically correlated with the ratios of TGF-α and TGF-β expression in these lobes (r=0.886, p<0.0001).In conclusion, these findings indicate that TGF-α and TGF-β expression increase in relation to hepatocyte proliferation and apoptosis, respectively after PVE in humans and the balance of the two factors may contribute to hepatic atrophy and hypertrophy concomitantly observed in this model.