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

大鼠尺寸错配肝移植模型中肝再生和萎缩相关基因的综合分析

基本信息

批准号：
15591385
负责人：
IMAMURA Hiroshi
金额：
$ 2.18万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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.

半肝门静脉栓塞（PVE）同时引起栓塞的肝叶萎缩和未栓塞的肝叶代偿性肥大。本研究的目的是评估PVE后生长刺激因子和抑制因子在这些肝叶中的作用。在PVE术后2 ~ 3周行肝切除术的10例患者，取栓塞和未栓塞的肝叶标本。采用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。免疫组化染色检测转化生长因子-α (TGF-α)和转化生长因子-β (TGF-β)的表达。PVE可诱导栓塞肺叶内肝细胞凋亡和未栓塞肺叶内肝细胞增殖。TGF-α在未栓塞肝叶肝细胞中的表达明显升高，TGF-α在栓塞肝叶中也有过表达，但表达适度。相比之下，栓塞肝叶肝细胞中TGF-β表达明显升高，未栓塞肝叶中TGF-β表达也升高，但程度较轻。PVE后未栓塞肺叶和栓塞肺叶的体积变化程度与肺叶中TGF-α和TGF-β的表达比有统计学意义（r=0.886, p<0.0001）。综上所述，上述结果提示，人PVE后，TGF-α和TGF-β的表达分别与肝细胞增殖和凋亡有关，两者的平衡可能与该模型中肝细胞萎缩和肥大有关。