Establishment of hepatic reserve function and molecular biological analysis of liver function after hepatectomy

肝切除术后肝储备功能的建立及肝功能的分子生物学分析

• 批准号: 12671235
• 负责人: CHIJIIWA Kazuo
• 金额: $ 1.92万
• 依托单位: Miyazaki Medical College (2002)Kyushu University (2000-2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671235/
• 关键词: Obstructive jaundice; Liver cirrhosis; Biliary drainage; Liver regeneration; Cyclin; Cyclin dependent kinase; Cell cycle; Transcriptional factor; 肝再生; 腸管内胆汁; 門脈結紮術; 萎縮; サイクリンE; 増殖因子; MAPキナーゼ; 転写因子C; EBP; 転写因子AP-1; 肝切除

1) We investigated the differences in the transcription factors and cell cycle regulators between obstructive jaundiced and control rats before and after hepatectomy. The expressions and activities of C/EBP-α and ?β were significantly decreased associated with the significantly lower cyclin E expression after hepatectomy in the jaundiced group than in the controls. The activities of AP-1, cyclin D1, and p21 were not significantly different between the two groups. These results suggest that obstructive jaundice inhibits hepatic expression and activities of C/EBP, resulting in the impaired cyclin E expression that is partly responsible for the cell cycle dysfunction after hepatectomy. (Reference 1)2) Regeneration responses in growth factor receptors, transcription factors, and cell cycle regulators after two-third hepatectomy were compared between rats with thioacetamide-induced cirrhotic and normal liver. The activities of C/EBP and AP- 1 were significantly inhibited in the cirrhotic gr … More oup compared with those in the control group, but not those of NF-kB and STAT 3. The expression of cyclin D1, E, and A was significantly decreased in the cirrhotic group compared with the control group. These results suggest that downregulation of cyclin D1, E, and A expression, which may be induced by impaired activities of C/EBP and AP-1, is responsible for the decreased regenerative capacity of cirrhotic liver after partial hepatectomy. (Reference 2)3) The importance of bile in liver regeneration after hepatectomy is known. Bile was drained externally (ED group) or into the duodenum (ID group) for 7 days before 70% hepatectomy, and liver regeneration was assessed by the relative liver weight, DNA synthesis rate, and PCNA labeling index. Posthepatectomy expressions of cyclin D1 and E, and cyclin D1- and E-associated kinase activity were also analyzed. Liver regeneration in the ED group was delayed than that in the ID group. Cyclin D1 and E expression and cyclin D1-associated kinase activity were not different between the two groups. Cyclin E-associated kinase activity was lower in the ID group than the ED group at 18 hr after hepatectomy. These results suggest the absence of intestinal bile delays liver regeneration associated with cyclin E-associated kinase inactivation after hepatectomy. (Reference 3) Less

1)我们研究了阻塞性黄疸大鼠和对照大鼠肝切除术前后转录因子和细胞周期调节因子的差异。C/EBP-α和？黄疸组肝切除术后细胞周期蛋白E的表达明显低于对照组。AP-1、cyclin D1和p21的活性在两组之间没有显著差异。这些结果表明，梗阻性黄疸抑制肝脏C/EBP的表达和活性，导致细胞周期蛋白E表达受损，这是部分负责肝切除术后细胞周期功能障碍。（参考文献1）2）在硫代乙酰胺诱导的肝硬化大鼠和正常肝脏之间比较了三分之二肝切除术后生长因子受体、转录因子和细胞周期调节因子的再生反应。C/EBP和AP- 1的活性在缺血性脑损伤中受到明显抑制。 ...更多信息 而NF-kB和STAT 3的表达与对照组无明显差异。与对照组相比，哮喘组细胞周期蛋白D1、E和A的表达显著降低。这些结果表明，下调细胞周期蛋白D1，E，和A的表达，这可能是由受损的C/EBP和AP-1的活动，是负责部分肝切除术后减少再生能力的肝硬化。（参考文献2）3）胆汁在肝切除术后肝再生中的重要性是已知的。在70%肝切除前，将胆汁外引流（艾德组）或十二指肠引流（ID组）7 d，通过相对肝重、DNA合成率和PCNA标记指数评估肝再生。同时分析术后细胞周期蛋白D1和E的表达，以及细胞周期蛋白D1和E相关激酶的活性。艾德组肝再生延迟。细胞周期蛋白D1和E的表达和细胞周期蛋白D1相关激酶活性在两组之间没有差异。肝切除术后18小时，ID组的细胞周期蛋白E相关激酶活性低于艾德组。这些结果表明，肝切除术后肠胆汁的缺乏延迟了与细胞周期蛋白E相关激酶失活相关的肝再生。（参考文献3）减

项目成果

Chijiiwa, K, et al.: "Relation of biliary bile acid output to hepatic ATP level and biliary indocyanine green excretion in humans"World Journal of Surgery. 26・4. 457-461 (2002)

Chijiiwa, K, et al.：“人类胆汁胆汁酸输出与肝脏 ATP 水平和胆汁吲哚菁绿排泄的关系”26・4 (2002)。

Chihiiwa K, et al.: "Biliray indocyanine green excretion as a predictor of hepatic adenosine triphosphate levels in patients with obstructive jaundice"American Jounal of Surgery. 179・2. 161-166 (2000)

Chihiiwa K 等人：“Biliray 吲哚菁绿排泄作为阻塞性黄疸患者肝三磷酸腺苷水平的预测因子”美国外科杂志 179・2 (2000)。

Saiki S,Chijiiwa K, et al.: "Preoperative internal biliary drainage is superior to external biliary darinage in liver regeneration and function after hepatectomy in obstructive jaundice."Annals of Surgery. 230・5. 655-662 (1999)

Saiki S、Chijiiwa K 等人：“对于梗阻性黄疸肝切除术后的肝再生和功能而言，术前胆汁内引流优于胆汁外引流。”Annals ofurgery 230・5 (1999)。

Nakano K, Todo T, Chijiiwa K, Tanaka M: "Therapeutic efficacy of G207, a conditionally-replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters"Molecular Therapy. 3(4). 431-437 (2001)

Nakano K、Todo T、Chijiiwa K、Tanaka M：“G207（一种条件复制型单纯疱疹病毒 1 型突变体）对免疫活性仓鼠胆囊癌的治疗效果”分子疗法。

Watanabe M, Chijiiwa K, et al.: "FR167653 improves survival and pulmonary injury after partial hepatectomy under ischemia/reperfusion in rats"Journal of Surgical Research. 101・2. 146-151 (2001)

Watanabe M、Chijiiwa K 等人：“FR167653 改善大鼠缺血/再灌注下部分肝切除术后的存活率和肺损伤”《外科研究杂志》101・2（2001 年）。