Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system

cDNA微阵列系统分析大鼠门静脉结扎后再生肝脏的基因表达谱

• 批准号: 13671324
• 负责人: SHIMADA Hiroshi
• 金额: $ 1.41万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671324/
• 关键词: liver regeneration; portal vein embolization; DNA microarray

Aims : We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group which had the same size liver but no PL.Methods : The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays. And the hepatic ATP level was measured.Results : The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, p<0.05). Gene expression of cyclin D1, PCNA, cyclin A and B was up-regulated, and the CDK inhibitor was down-regulated. Increases were observed in : (i) pyruvate dehydrogenase, the TCA cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48±0.01μmol/ml vs. 0.33±0.01μmol./ml, p<0.05).Conclusion : The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism. Key words : liver regeneration, portal vein embolization, extended hepatectomy, DNA microarray, hepatic ATP level.

目的：我们评估了门静脉结扎（PL）后，在一个测试组的大鼠与对照组，有相同大小的肝脏，但没有PL的基因表达的变化。方法：门静脉左叶和中叶的测试组结扎在初始操作。PL后4天，后尾状叶的肝脏体积（5%）增加了2倍，占肝脏的10%。然后进行90%的肝切除术，仅留下肥大的尾状叶后叶，并在对照组（假手术）中留下正常的前后尾状叶（10%）。使用cDNA微阵列比较两组之间的表达谱。结果：肝切除术后4d，PL组大鼠存活率为56.3%，明显高于假手术组的26.7%（P<0.05）; cyclin D1、PCNA、cyclin A和B基因表达上调，CDK抑制因子表达下调。观察到以下方面的增长：（i）丙酮酸脱氢酶，TCA循环调节剂，（ii）酰基辅酶A脱氢酶，氧化调节剂，和（iii）细胞色素氧化酶，氧化磷酸化调节剂。肝切除术后，PL组肝ATP浓度维持较好（0.48±0.01μmol/ml vs.0.33 ±0.01 μmol/ml），而假手术组肝ATP浓度维持较好（0.48±0.01μmol/ml vs.0.33 ±0.01μmol/ml）。结论：再生肝对扩大肝切除的耐受性较正常肝增强。据信，这是因为肝切除术后剩余肝脏的诱导快速再生增加了ATP代谢。关键词：肝再生，门静脉栓塞，扩大肝切除，DNA微阵列，肝ATP水平。

项目成果

Nagano Y., Shimada H.et al.: "Improve functional reserve of hypertrophied contra lateral liver after portal vein ligation in rats"J. Hepatology. 37(7). 72-77 (2002)

Nagano Y.，Shimada H.et al.：“改善大鼠门静脉结扎后肥大的对侧肝脏的功能储备”J。

Nagano Y, Shimada H et al.: "Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system"Liver International. (In Press).

Nagano Y、Shimada H 等人：“通过 cDNA 微阵列系统对大鼠门静脉结扎后再生肝脏进行基因表达谱分析”肝脏国际。

Nagano Y: "Improved functional reserve of hypertrophied contra lateral liver after portal vein ligation in rats"J.Hepatology. 37(7). 72-77 (2002)

Nagano Y：“大鼠门静脉结扎后肥大的对侧肝脏的功能储备得到改善”J.Hepatology。

Nagano Y, Shimada H et al.: "Improved functional reserve of hypertrophied contra lateral liver after portal vein ligation in rats"J.Hepatology. 37(7). 72-77 (2002)

Nagano Y、Shimada H 等人：“大鼠门静脉结扎后肥大的对侧肝脏的功能储备得到改善”J.Hepatology。

Nagano Y: "Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system"Liver International. (In press).

Nagano Y：“通过 cDNA 微阵列系统对大鼠门静脉结扎后再生肝脏进行基因表达谱分析”肝脏国际。