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：我们评估了实验组大鼠门静脉结扎 (PL) 后肥大肝脏基因表达的变化，并与具有相同大小肝脏但无 PL 的对照组进行比较。方法：左叶和正中叶的门静脉在 PL 后四天进行结扎的测试组中，后尾状叶的肝脏体积 (5%) 增加了两倍，占肝脏的 10%。然后进行肝切除术，仅保留肥大的后尾状叶，并在对照组（假手术组）中保留正常的前尾状叶和后尾状叶（10%），使用cDNA微阵列对两组之间的表达谱进行比较。测量肝脏 ATP 水平。结果：肝切除术后 4 天，PL 组的存活率显着高于假手术组（56.3% 和26.7%，p<0.05) 细胞周期蛋白 D1、PCNA、细胞周期蛋白 A 和 B 的基因表达上调，而 CDK 抑制剂的基因表达下调：(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。肝切除后，PL 组比假手术组更好地维持了肝脏 ATP 浓度（0.48±0.01μmol/ml vs. 0.33±0.01μmol./ml，p<0.05）。结论：再生肝脏对扩大肝切除术的耐受性增强。据认为，这是因为肝切除后剩余肝脏的快速再生增加了 ATP 代谢。静脉栓塞、扩大肝切除术、DNA 微阵列、肝脏 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。

Morita T., Shimada H.et al.: "Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray"J. Hepatobiliary Pancreat Surg. 9. 352-359 (2002)

Morita T.、Shimada H.等人：“使用 cDNA 微阵列研究过度肝切除术后肝衰竭的机制”J.

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。