基础医学与临床 ›› 2014, Vol. 34 ›› Issue (7): 945-949.

• 研究论文 • 上一篇    下一篇

塞来昔布诱导人椎间盘细胞表达神经生长因子

陈小明1,周润梅2,欧斌1,曹奇1   

  1. 1. 南华大学附属第二医院
    2. 南华大学药学与生命科学学院药物药理研究所
  • 收稿日期:2013-10-08 修回日期:2014-01-14 出版日期:2014-07-05 发布日期:2014-06-24
  • 通讯作者: 周润梅 E-mail:zhourunmei@126.com
  • 基金资助:
    湖南省科技计划项目

Celecoxib induces intervertebral disc cells expression of nerve growth factor

  • Received:2013-10-08 Revised:2014-01-14 Online:2014-07-05 Published:2014-06-24

摘要: 目的 研究环氧化酶2抑制剂塞来昔布以及前列腺素E2(PGE2)对神经生长因子(NGF)表达的影响。方法 分离培养人椎间盘(IVD)细胞,用不同浓度的塞来昔布预处理30min后,加入10ng/ml IL-1β作用6h。RT-PCR和ELISA分别检测NGF mRNA和蛋白的表达,ELISA检测PGE2的分泌。同时加入外源性PGE2以及其受体(EPs 1~4)激动剂,观察其对NGF产生的影响。结果 IL-1β作用3h即可以一定的时间依赖性诱导IVD细胞表达NGF mRNA。塞来昔布处理后能使NGF mRNA水平进一步增加1.8倍。IL-1β处理后,PGE2含量达(5.46±0.64)ng/mL。10mmol/L塞来昔布能将其降低至(1.07±0.04)ng/mL(P<0.05)。IVD细胞经100μmol/L PGE2处理后,IL-1β诱导的NGF降低了59%(P<0.05)。此外,采用EP2和EP4受体激动剂处理IVD细胞后,也得到了类似的结果,而EP1和EP3激动剂处理对NGF产生无明显影响。结论 塞来昔布能促进IVD细胞表达NGF,其机制可能与抑制PGE2的分泌有关。

关键词: 神经生长因子, 椎间盘细胞, 前列腺素E2, 塞来昔布

Abstract: Objective To investigate the effect of a selective COX-2 inhibitor Celecoxib and PGE2 on expression of nerve growth factor (NGF). Methods Isolated human IVD cells were stimulated with 10ng/ml of IL-1β in the presence or absence of different concentration of Celecoxib. NGF expression and paoduction were determined by real-time PCR and ELISA, respectively. Secretion of PGE2 was determined by ELISA. The effects of exogenous PGE2 and its receptor (EPs1-4) agonists were also tested for NGF production. Results Stimulation of IL-1β for 3h could induce IVD cells to express NGF mRNA in a dose-dependent manner. Pre-treatment with Celecoxib strongly enhanced it to 1.8 fold. 10ng/mL of IL-1β induced PGE2 production to (5.46±0.64)ng/mL, At the concentration of 10mmol/L Celecoxib, PGE2 release was substantially inhibited to (1.07±0.04) ng/mL (P<0.05). 100μmol/L PGE2 inhibited IL-1β induction of NGF to 59% (P<0.05), and this effect was mimicked when agonists EP2 and EP4, but not EP1 and EP3, were supplemented to the culture. Conclusion. Celecoxib can enhance IL-1β-induced NGF expression, and this effect may be mediated by inhibition of PGE2 production.

Key words: Nerve growth factor, intervertebral disc cells, prostaglandin E2, Celecoxib

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