Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-α-deficient mice
Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-α-deficient mice
复制标题
DOI：
10.1111/j.1478-3231.2005.01029.x
复制
发表时间：
2005-02-01
影响因子：
6.7
通讯作者：
Moriwaki, H
中科院分区：
文献类型：
--
作者：
Hayashi, H;Nagaki, M;Moriwaki, H
目的/背景：肿瘤坏死因子- α (tnf - α)被认为是一种促炎细胞因子，在许多疾病过程中被认为是一个促成因素。tnf - α也影响肝毒性损伤后的肝脏修复和部分肝切除术后的肝脏再生。本研究的目的是评估tnf - α影响PH后tnf - α缺陷（tnf - α(-/-)）小鼠肝细胞凋亡和再生的机制。方法：对野生小鼠和tnf - α(-/-)小鼠进行PH测定。结果：两组血清丙氨酸转氨酶和血清总胆红素水平分别在PH后6和48 h达到峰值。通过有丝分裂和增殖细胞核抗原标记指数测定，tnf - α(+/+)和tnf - α(-/-)小鼠的肝细胞增殖没有差异。在两种类型的小鼠中均未见末端脱氧核苷酸转移酶缺口末端标记阳性的肝细胞。PH后tnf - α(-/-)小鼠剩余肝脏中核因子- kappab DNA结合活性与对照小鼠相似。核糖核酸酶保护实验结果显示，两组小鼠肝脏中转化生长因子β 1 mRNA的表达水平均明显上调，而其他细胞因子的表达水平基本不存在。tnf - α(-/-)小鼠的白细胞介素-6/信号换能器和转录-3依赖通路的激活因子不受影响。结论：提示tnf - α对小鼠PH后肝脏再生和肝细胞凋亡影响不大。
Aims/Background: Tumor necrosis factor-alpha (TNF-alpha) is known as a proinflammatory cytokine that has been implicated as a contributing factor in a number of disease processes. TNF-alpha also influences liver repair following hepatotoxic damage, and regeneration following partial hepatectomy (PH). The aim of this study was to assess the mechanism by which TNF-alpha influences liver cell apoptosis and regeneration following PH in TNF-alpha-deficient (TNF-alpha(-/-)) mice. Methods: PH was performed in wild mice and TNF-alpha(-/-) mice. Results: In both groups, serum alanine aminotransferase and serum total bilirubin levels comparably peaked at 6 and 48 h after PH, respectively. No differences were observed in hepatocyte proliferation, as determined by mitotic and the proliferating cell nuclear antigen labeling indices, between TNF-alpha(+/+) and TNF-alpha(-/-) mice. Few terminal deoxynucleotidyl transferase nick end-labeling-positive hepatocytes were seen in either type of mice. Nuclear factor-kappaB DNA binding activity in the remaining liver of TNF-alpha(-/-) mice after PH was similar to that of control mice. Ribonuclease protection assay showed that transforming growth factor beta1 mRNA was up-regulated comparably in the livers of the two groups, and that other cytokines were hardly seen in either. Interleukin-6/ signal transducer and activator of transcription-3-dependent pathway was not affected in TNF-alpha(-/-) mice. Conclusions: These findings suggest that TNF-alpha has little influence on liver regeneration and liver cell apoptosis after PH in mice.