Transfection of NF-kB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

将 NF-kB 诱饵寡脱氧核苷酸转染至巨噬细胞可减少过度肝切除术后小鼠致命性肝衰竭

• 批准号: 18591521
• 负责人: TOGO Shinji
• 金额: $ 2.45万
• 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: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591521/
• 关键词: Ecessive hepatectomy; cytokine; NF-kB; apoptosis; liver regeneration; IL-6; TN-α

Background: Macrophages play an important role in the initiation of the hypercytokinemia that is involved in the development of liver failure after excessive hepatectomy. This study was aimed at evaluating whether the selective suppression of NF-kB in macrophages by decoy oligodeoxynucleotides (ODN) could prevent liver failure after excessive hepatectomy. Materials and Methods: Ninety-percent hepatectomy was performed in 8-week-old mice. NF-KB/decoy/ODN was transfected into the liver by the HVJ-liposome method. The survival rate, serum levels of IL-18, IL-6 and TNF-a, and the histological findings in the remnant liver were compared between the 90%-hepatectomized mice transfected with the decoy ODN (decoy group) and the 90%-hepatectomized mice injected with saline (control group) . Result: The control group mice died within 48 hours of the operation, while the survival rate in the decoy group at 48 hours after the operation was 35%, and at 2 weeks, 15%. The serum levels of all cytokines were significantly lower in the decoy group than in the control group. The number of TUNEL-positive cells in the remnant liver was smaller in the decoy group. Conclusion: Transfection of NF-kB/decoy/ODN reduces fatal liver failure in mice after excessive hepatectomy by suppressing hypercytokinemia, but offers only a low rate of survival.(199 words)

背景：巨噬细胞在过度肝切除后高细胞分裂素血症的发生中起重要作用，高细胞分裂素血症参与肝功能衰竭的发生。本研究旨在评价诱骗寡核苷酸(ODN)选择性抑制巨噬细胞中的核因子-kB是否能预防过度肝切除后的肝功能衰竭。材料和方法：取8周龄小鼠90%的肝切除。用HVJ-脂质体方法将核因子-KB/圈套/ODN导入肝脏。比较两组小鼠的存活率、血清IL-18、IL-6、TNF-α水平及肝组织学改变。结果：对照组小鼠在术后48h内死亡，诱骗组术后48h存活率为35%，术后2周存活率为15%。诱骗组小鼠血清中所有细胞因子水平均显著低于对照组。诱骗组大鼠残肝组织中TUNEL阳性细胞数较少。结论：转导核因子-kB/圈套/ODN可通过抑制高细胞因子血症而减少过度肝切除后小鼠的致死性肝衰竭，但存活率较低。

项目成果

PAI-1 plays an important role in liver failure after excessive hepatectomy in the rat

• DOI: 10.1016/j.jss.2007.04.041
• 发表时间: 2007-11-01
• 期刊: JOURNAL OF SURGICAL RESEARCH
• 影响因子: 2.2
• 作者: Watanabe, Kazuteru;Togo, Shinji;Shimada, Hiroshi
• 通讯作者: Shimada, Hiroshi

Transfection of NF-kB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

将 NF-kB 诱饵寡脱氧核苷酸转染至巨噬细胞可减少过度肝切除术后小鼠致命性肝衰竭

• 期刊: J Surg Res (in press)
• 作者: Takahashi;T;Togo;S;Kumamoto;T;Watanabe;K;Kubota;T;Ichikawa;Y;Endo;I;Kunisaki;C;Nagashima;Y;Fujimoto;J;Shimada;H
• 通讯作者: H

Transfection of NF-xB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy

将 NF-xB 诱饵寡脱氧核苷酸转染至巨噬细胞可减少过度肝切除术后小鼠致命性肝衰竭

• 期刊: J Surg Res (in press)
• 作者: Takahashi T;Togo S;et. al.
• 通讯作者: et. al.

Transfection of NF-kB decoy oligodeoxynucleotides into macro phages reduces murine fatal liver failure after excessive hepatectomy

将 NF-kB 诱饵寡脱氧核苷酸转染到巨噬细胞中可减少过度肝切除术后小鼠致命性肝衰竭

• 期刊: J Surg Res (in press)
• 作者: Takahashi T;Togo S;et. al.
• 通讯作者: et. al.

Safety limit of extent of hepatectomy for rats with moderately fatty liver : Experimental study concerning libing liver donor surgery.

中度脂肪肝大鼠肝切除范围的安全限度：解放肝供体手术的实验研究。

• 发表时间: 2006
• 期刊: J of Gastroenterology and Hepatology 21
• 作者: Morioka D;Togo S et al.
• 通讯作者: Togo S et al.