中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (5): 769-773.doi: 10.3969/j.issn.1673-8225.2011.05.003

• 肝移植 liver transplantation • 上一篇    下一篇

NF-κB参与低氧预适应对自体原位肝移植大鼠JNK通路的影响

孟中良1，张培建1，伍学艳1，庄卓男1，张  杰1，苏  辉1，蒋永军1，金  成2   

  1. 1扬州大学第二临床医学院普通外科研究室，江苏省扬州市 225000
    2无锡市第三医字肝胆胰中心，江苏省无锡市  214000
  • 收稿日期:2010-08-23 修回日期:2010-11-13 出版日期:2011-01-29 发布日期:2011-01-29
  • 通讯作者: 张培建，硕士，教授，主任医师，硕士生导师，主要从事肝胆胰外科疾病的临床基础与应用研究。 yzu.edu.pjz@163.com
  • 作者简介:孟中良★，男，1985生，江苏省江阴市人，汉族，扬州大学第二临床医学院在读硕士，主要从事肝胆胰外科疾病的基础与临床研究。 mzl913@163.com
  • 基金资助:

    江苏省卫生厅科研课题(H200770)，课题名称：低氧预适应后肠道缺氧诱导因子1α表达与移植肝功能的相关性的研究。江苏省扬州市科技攻关项目(YZ2008042)，课题名称：缺氧诱导因子1介导的移植肝大鼠肝窦内皮细胞保护的机制研究。2010年无锡市社会发展科技指导性计划项目，课题名称：缺氧诱导因子1价导的AP法对肝窦内皮细胞的影响及其相关信号传导通路的调控。

Nuclear factor kappa B participates in hypoxia preconditioning influencing JNK pathway in rat orthotopic liver transplantation 

Meng Zhong-liang1, Zhang Pei-jian1, Wu Xue-yan1, Zhuang Zhuo-nan1, Zhang Jie1, Su Hui1, Jiang Yong-jun1, Jin Cheng2   

  1. 1Institute of General Surgical Research, Second Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
    2Center of Liver, Gall and Pancreas, Wuxi Third Hospital, Wuxi  214000, Jiangsu Province, China
  • Received:2010-08-23 Revised:2010-11-13 Online:2011-01-29 Published:2011-01-29
  • Contact: Zhang Pei-jian, Master, Professor, Chief physician, Master’s supervisor, Institute of General Surgical Research, Second Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China yzu.edu.pjz@163.com
  • About author:Meng Zhong-liang★, Studying for master’s degree, Institute of General Surgical Research, Second Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China mzl913@163.com
  • Supported by:

    the Science and Technology Subjects of Healthy Department of Jiangsu Province, No. H200770*; the Tackle Key Program in Science and Technology of Jiangsu Province, No. YZ2008042*; the Science and Technology Plan for Society Development of Wuxi City*

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摘要：

背景：在肝脏缺血再灌注损伤中，NF-κB与JNK通路的串扰方式决定了细胞的死亡或存活。而将低氧预适应用于肝移植过程所导致的细胞凋亡现象，尚未见有报道。
目的：探讨低氧预适应后NF-κB的表达对移植肝JNK通路的影响及保护作用。
方法：采用经门静脉灌注法建立大鼠自体原位肝移植模型，SD大鼠随机分为正常对照组：不接受任何处理；自体移植组：行自体原位肝移植；低氧预适应组：移植前体积分数8%氮氧混合气体的低氧预处理90 min，然后行自体原位肝移植。分别于移植后 1，6，24 h处死大鼠取肝脏标本检测肝组织丙二醛、超氧化物歧化酶水平，免疫组化方法测定大鼠肝组织p-JNK蛋白，RT-PCR检测肝脏 NF-κB mRNA含量，透射电子显微镜下观察肝细胞的超微结构变化。
结果与结论：与对照组比较，两移植组肝组织丙二醛水平升高，超氧化物歧化酶水平降低(P < 0.05)；与自体移植组比较，低氧预适应组丙二醛水平显著降低、超氧化物歧化酶水平显著升高(P < 0.05)。与正常对照组比较，两移植组各时相p-JNK蛋白的表达、NF-κB mRNA的转录水平显著升高 (P <0.05)；与自体移植组比较，低氧预适应组NF-κB mRNA转录水平显著增高(P < 0.05)，p-JNK蛋白的表达明显降低(P < 0.05)。透射电镜下自体移植组肝细胞出现典型的凋亡征象，而低氧预适应组肝细胞无明显凋亡形态。提示，肝移植大鼠低氧预适应后可能通过上调NF-κB的表达，减少活性氧释放，抑制JNK通路的持续激活，从而抑制肝细胞凋亡，减轻肝脏缺血再灌注。

关键词: 低氧预适应, 肝移植, 活性氧, NF-&kappa, B, JNK, 缺血再灌注损伤

Abstract:

BACKGROUND: Nuclear factor κB (NF-κB) and JNK cascade pathway determine the fate of cells in liver ischemia/reperfusion injury. However, there are few reports addressing hypoxia preconditioning-reduces apoptosis during liver transplantation. 
OBJECTIVE: To assess the role and protective effects of NF-κB on JNK pathway mediated by hypoxia preconditioning.
METHODS: An orthopotic liver transplantation model was constructed by portal vein perfusion. SD rats were randomly divided into the following three groups: normal control group: received no treatment; autotransplantation group: performed autotransplantation; and hypoxia preconditioning group: rats were given an 8% oxygen mixed gas for 90 minutes before autotransplantation. At 1, 6 and 24 hours after operation, rats were sacrificed for detection of p-JNK protein, malondialdehyde and superoxide dismutase (SOD) expressions. NF-κB mRNA content was detected by RT-PCR, and the ultrastructure changes of hepatocytes were observed under a transmission electron microscopy. 
RESULTS AND CONCLUSION: Compare to the normal control group, the expression of malondialdehyde level was significant increased, but SOD was obviously decreased (P < 0.05) in the transplantation groups. Compare to the autotransplantation group, the expression of malondialdehyde was decreased significantly, and SOD was increased significantly in the hypoxia preconditioning group (P < 0.05). The expression of p-JNK protein and NF-κB mRNA in the transplantation groups were dramatically increased compared with normal control group (P < 0.05). The NF-κB mRNA level was increased but p-JNK protein expression decreased in the hypoxia preconditioning group compared with autotransplantation group (P< 0.05). Hepatic cells in the autotransplantation group showed typical apoptosis sign under transmission electron microscope, but no apoptosis was found in the hypoxia preconditioning group. The findings demonstrated that hypoxia preconditioning has marked inhibition to apoptosis by upregulating protein expression of NF-κB, preventing reactive oxygen species accumulation and suppressing prolonged JNK activation after orthopotic liver transplantation.

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