中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (53): 9977-9981.doi: 10.3969/j.issn.1673-8225.2010.53.024

• 器官移植基础实验 basic experiments of organ transplantation • 上一篇    下一篇

SP600125对大鼠肝缺血再灌注损伤的保护作用

仇爱刚1,徐三荣2,李  杰2,张海鸣2,顾小海1   

  1. 1江苏大学临床医学院,江苏省镇江市  212013;  2江苏大学附属医院普外科,江苏省镇江市  212001
  • 出版日期:2010-12-31 发布日期:2010-12-31
  • 通讯作者: 徐三荣,主任医师,硕士生导师,江苏大学附属医院普外科,江苏省镇江市 212001 zjxsrong@163.com
  • 作者简介:仇爱刚★,男,1984年生,江苏省盐城市人,汉族,2010年江苏大学临床医学院毕业,硕士,主要从事肝胆外科方面的研究。 qiuaigang@163.com
  • 基金资助:

    镇江市社会发展基金资助项目(sH2007021)“VEGF在肝脏缺血再灌注损伤中的表达以及干预研究”。负责人:徐三荣博士。

Protective effect of SP600125 on hepatic ischemia/reperfusion injury in rats

Qiu Ai-gang1, Xu San-rong2, Li Jie2, Zhang Hai-ming1, Gu Xiao-hai1   

  1. 1 College of Clinical Medicine, Jiangsu University, Zhenjiang  212013, Jiangsu Province, China; 2 Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang  212001, Jiangsu Province, China
  • Online:2010-12-31 Published:2010-12-31
  • Contact: Xu San-rong, Chief physician, Master’s supervisor, Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China zjxsrong@163.com
  • About author:Qiu Ai-gang★, Master, College of Clinical Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China qiuaigang@163.com
  • Supported by:

    the Foundation for Society Development of Zhenjiang City, No. sH2007021*

摘要:

背景:SP600125作为JNK激酶抑制剂,可特异性阻断JNK细胞转导通路,对肝脏缺血再灌注又起到怎样的作用,目前尚无相关研究。
目的:应用SP600125对肝脏缺血再灌注进行干预,分析JNK信号转导通路在该病理生理过程中的作用。
方法:将30只雄性SD大鼠按随机数字表法分为3组,假手术组、缺血再灌注组及SP600125组各10只。假手术组仅行进腹手术;缺血再灌注组行进腹手术,阻断肝左中叶的血供;SP600125组于术前半小时腹腔注射SP600125 15 mg/kg,其他操作同缺血再灌注组。于复灌后2 h取材,分别测定各组血清肝功能酶活性,通过苏木精-伊红切片染色观察肝组织结构的病理变化,运用免疫组织化学法检测肝组织中p-JNK表达并进行半定量分析,以比色法检测肝脏丙二醛含量及髓过氧化物酶活性。
结果与结论:相对于缺血再灌注组,SP600125组血清肝功能酶活性明显下降,肝脏p-JNK表达较低,肝脏髓过氧化物酶活性以及丙二醛含量下降,病理损伤有所缓解。提示JNK细胞信号转导通路在肝缺血再灌注损伤过程中被广泛激活,应用JNK抑制剂SP600125对缺血再灌注损伤有保护作用。

关键词: 缺血再灌注损伤, 肝脏, JNK, SP600125, 信号转导, 保护

Abstract:

BACKGROUND: As JNK kinase inhibitor, SP600125 can specific and selective block JNK signal transduction pathways. However, it is poorly understood the role of SP600125 on hepatic ischemia/reperfusion (IR) injury.
OBJECTIVE: SP600125 was used to interfere in hepatic IR injury and to analyze the mechanism of JNK signaling pathway in this process.
METHODS:Thirty normal male Sprague-Dawley rats were randomly divided into sham operation group, IR group and JNK inhibitor SP600125 group. The left medius lobe was blocked in the IR group. At half hour before operation, 15 mg/kg SP600125 were injected into rats in the SP600125 group. All rats were killed at 2 hours after reperfusion. Routine assays were performed for testing the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); the pathological changes in the liver was evaluated with hematoxylin-eosin staining and contents of maleicdialdehyde (MDA) and myeloperoxidase (MPO) in liver tissues were detected by colorimetric method.
RESULTS AND CONCLUSION: Compared to the IR group, the levels of serum ALT, AST, contents of MPO and MDA, as well as expression of p-JNK in hepatic tissues decreased significantly in the SP600125 group. The pathological changes of hepatic IR injury could be alleviated obviously. The activation of JNK signal pathway plays a pivotal role in hepatic IR injury, which can be alleviated by SP600125 treatment.

中图分类号: