Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray.
Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray.
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DOI：
10.1007/s005340200039
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Shimada, Hiroshi
中科院分区：
文献类型：
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作者：
Morita, Tomoyuki;Togo, Shinji;Shimada, Hiroshi
背景/目的：过度的肝切除术常常导致致命的肝功能衰竭。我们报道这主要是由细胞凋亡介导的，其病理学特征是末端脱氧核苷酸转移酶介导的 dUTP-生物素缺口末端标记 (TUNEL) 检测阳性肝细胞和 DNA 片段化检测中的阶梯模式。 方法：为了研究其机制，我们使用 cDNA 微阵列分析来比较明显分化的大鼠部分肝切除 (PHx) 模型（90% PHx 和 95% PHx）。所有90%的PHx大鼠均存活，但95%的PHx动物在96小时内死于肝衰竭。在四个时间点（PHx 后 1、3、12 和 24 小时）获得残余肝脏。 RNA 提取后，两个样品用不同的荧光染料标记，并与理化研究所 (RIKEN) 的 18 816 个全长富集小鼠 cDNA 阵列杂交。扫描荧光染料信号，并检测两种模型的mRNA表达比。结果：95% PHx组中，p21细胞周期蛋白依赖性激酶（CDK）抑制剂、Fas、白细胞介素（IL）-18和许多caspases基因在PHx后1 h表达上调。另一方面，Bcl-2、热休克蛋白和谷胱甘肽-S-转移酶基因下调。结论：我们得出结论，过度肝切除术后致命性肝衰竭的特点是细胞凋亡增加和肝再生减少。
BACKGROUND/PURPOSE: Excessive hepatectomy often causes fatal liver failure. We have reported that this is mainly mediated by apoptosis, characterized pathologically by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) assay-positive hepatocytes and a ladder pattern in DNA fragmentation assays.METHODS: To investigate the mechanism, we used cDNA microarray analysis to compare clearly differentiated rat partial hepatectomy (PHx) models (90% PHx, and 95% PHx). All 90% PHx rats survived, but the 95% PHx animals died of hepatic failure within 96 h. Remnant liver was obtained at four time points (1, 3, 12, and 24 h after PHx). After RNA extraction, two samples were labeled with different fluorescent dyes and hybridized to the Institute of Physical and Chemical Research (RIKEN) set of 18 816 full-length enriched mouse cDNA arrays. Scanning for fluorescent dye signals was performed, and the mRNA expression ratio of the two models was examined.RESULTS: Genes of the p21 cyclin-dependent kinase (CDK) inhibitor, Fas, interleukin (IL)-18, and many caspases were upregulated at 1 h after PHx in the 95% PHx group. On the other hand, genes of Bcl-2, heat shock proteins, and glutathione-S-transferase were downregulated.CONCLUSIONS: We concluded that fatal hepatic failure after excessive hepatectomy was characterized by increased apoptosis and diminished liver regeneration.