《中国康复理论与实践》

《中国康复理论与实践》 ›› 2013, Vol. 19 ›› Issue (4): 341-345.

• 基础研究 • 上一篇    下一篇

c-Jun 氨基末端激酶信号通路抑制对白细胞介素-1诱导的大鼠椎间盘纤维环细胞基因表达的影响

原威，王以朋，吴志宏，于斌   

  1. 中国医学科学院，北京协和医学院，北京协和医院骨科，北京市100730
  • 收稿日期:2012-12-28 修回日期:1900-01-01 出版日期:2013-04-25 发布日期:2013-04-25

Effect of c-Jun N-terminal Kinase Inhibition on Gene Expression Induced by Interleukin-1 in Annulus Fibrosus Cells in Rats

YUAN Wei, WANG Yi-peng, WU Zhi-hong, et al   

  1. Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Beijing 100730, China
  • Received:2012-12-28 Revised:1900-01-01 Published:2013-04-25 Online:2013-04-25

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摘要： 目的　研究c-Jun 氨基末端激酶(JNK)信号通路抑制对白细胞介素-1(IL-1)诱导的大鼠椎间盘纤维环细胞基因表达的影响，为阻止椎间盘退变提供新的治疗靶点。方法　分离培养大鼠尾椎纤维环细胞，IL-1 刺激纤维环细胞后，Western blot 检测JNK信号通路的激活；传代的纤维环细胞培养48 h 后，以IL-1(10 ng/ml)加或不加JNK通路抑制剂SP600125 刺激24 h，Real-Time PCR检测JNK通路抑制对IL-1 诱导的大鼠纤维环细胞基因表达的影响。结果　JNK通路抑制可显著抑制IL-1 引起的诱导性一氧化氮合酶(iNOS)、白细胞介素-6(IL-6)、环氧合酶-2(Cox-2)和基质金属蛋白酶(MMP)-3、MMP-13 表达上调，同时，可显著逆转IL-1 引起的Ⅰ型胶原和胰岛素样生长因子-1(IGF-1)基因表达下调。结论　JNK通路抑制可作为阻断IL-1 诱导的椎间盘退变的治疗靶点。

关键词: 纤维环细胞, 信号转导, c-Jun 氨基末端激酶, 白细胞介素-1, 大鼠

Abstract: Objective To determine the role of c-Jun N-terminal kinase (JNK) signaling in annulus fibrosus cells response to interleukin (IL)-1. Methods Rat annulus fibrosus cells cultured in monolayer were exposed to IL-1, with or without JNK inhibition by SP600125. RNA was isolated for Real-Time polymerase chain reaction (PCR) after 24 h stimulation. Results IL-1 upregulation of mRNA for inducible nitric oxide synthase (iNOS), IL-6, cyclooxygenase (Cox)-2, matrix metalloproteinase (MMP)-3, MMP-13 were blunted by JNK inhibition, while downregulation of collagenⅠand insulin-like growth factor (IGF)-1 were also reversed by JNK inhibition. Conclusion JNK signaling inhibition can be a therapeutic target for blocking intervertebral disc degeneration induced by IL-1.

Key words: annulus fibrosus cells, signal transduction, c-Jun N-terminal kinase, interleukin-1, rats