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活体供者部分肝切除术后即刻的基因表达谱——肝脏再生的初始反应

Gene expression profiles in living donors immediately after partial hepatectomy - the initial response of liver regeneration.

作者信息

Ho Cheng-Maw, Lee Po-Huang, Lai Yeun-Tyng, Hu Rey-Heng, Ho Ming-Chih, Wu Yao-Ming

机构信息

Department of Surgery, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.

出版信息

J Formos Med Assoc. 2007 Apr;106(4):288-94. doi: 10.1016/S0929-6646(09)60254-0.

Abstract

BACKGROUND/PURPOSE: Gene expression profiles of liver regeneration are well explored in rat models. However, there are limited relative data in humans. This study aimed to show that mRNA expression profiles change immediately after right hepatectomy in living-related donors and correlate with mechanisms of liver regeneration reported in the literature.

METHODS

Prospective study was conducted from March 2003 to August 2004. Living-related donors who donated right lobe of liver were included. Liver biopsies were performed at the beginning and, 5 hours later, at the end of liver resection. RNAs were isolated to synthesize cRNA. Oligo DNA microarray experiments were conducted and paired signal intensity ratios (Cy3/Cy5) were normalized with rank-invariant global Lowess regression analysis by taking base two logarithms. Genes whose average residuals more than 2.5-fold increased or less than -2.5-fold decreased were selected to get the most pronounced expression changes during this period.

RESULTS

Five of 34 donors were included with qualified samples. The expression patterns of paired DNA microarray experiments were similar in five donors. A total of 28 upregulated and 14 downregulated genes were collected. Acute-phase proteins (serum amyloid A, complement-reactive protein, heme oxygenase-1) were upregulated. Genes related to growth signal transduction (G-protein coupled receptor-30) were downregulated.

CONCLUSION

Gene expression profiles immediately after partial hepatectomy were reported first in humans with the techniques of oligo DNA microarray, which were compatible with the initial gene expression patterns of liver regeneration in rats.

摘要

背景/目的:肝再生的基因表达谱在大鼠模型中已得到充分研究。然而,人类相关数据有限。本研究旨在表明,活体肝移植供体右半肝切除术后,mRNA表达谱立即发生变化,并与文献报道的肝再生机制相关。

方法

2003年3月至2004年8月进行前瞻性研究。纳入捐献右半肝的活体肝移植供体。在肝切除开始时、5小时后及结束时进行肝活检。分离RNA以合成cRNA。进行寡核苷酸DNA微阵列实验,并通过以2为底取对数的秩不变全局局部加权回归分析对配对信号强度比(Cy3/Cy5)进行标准化。选择平均残差增加超过2.5倍或减少超过-2.5倍的基因,以获得此期间最显著的表达变化。

结果

34名供体中有5名获得合格样本。5名供体的配对DNA微阵列实验表达模式相似。共收集到28个上调基因和14个下调基因。急性期蛋白(血清淀粉样蛋白A、补体反应蛋白、血红素加氧酶-1)上调。与生长信号转导相关的基因(G蛋白偶联受体-30)下调。

结论

首次利用寡核苷酸DNA微阵列技术报道了人类部分肝切除术后立即出现的基因表达谱,其与大鼠肝再生的初始基因表达模式相符。

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