基础医学与临床 ›› 2017, Vol. 37 ›› Issue (5): 668-675.

• 研究论文 • 上一篇    下一篇

IL-1β通过JAK2-STAT3促进大鼠脊髓损伤后胶质瘢痕形成

刘敬贤,夏永智,王富贵,唐维,晏怡   

  1. 重庆医科大学附属第一医院
  • 收稿日期:2017-01-03 修回日期:2017-03-15 出版日期:2017-05-05 发布日期:2017-04-19
  • 通讯作者: 晏怡 E-mail:yanyi2005@vip.sina.com
  • 基金资助:
    国家自然科学基金资助项目;重庆市自然科学基金资助项目;国家临床重点专科建设经费资助项目

IL-1β promotes glial scar formation after spinal cord injury in rats via JAK2-STAT3

  • Received:2017-01-03 Revised:2017-03-15 Online:2017-05-05 Published:2017-04-19

摘要: 目的 探讨IL-1β促进脊髓损伤后胶质瘢痕形成的机制。方法 将大鼠随机分为模型组(采用钳夹脊髓的方法建立SCI模型)、假手术组(sham group)、IL-1β特异性抑制剂组(IL-1RA)、IL-1β组(IL-1β)及IL-1β+JAK2-STAT3特异性抑制剂组(IL-1β+AG490)。假手术组只打开椎板,不作其他处理。在术后相应时间点(术后8及12 h和1、3、7及14 d)进行大鼠后肢BBB评分,用Western blot、免疫荧光和免疫组化技术检测GFAP、vimentin、P-STAT3的表达变化。 结果 P-STAT3(术后第8 h和第12 h)及GFAP、 vimentin(术后第7和第14天)表达趋势:模型组显著高于假手术组(p<0.01),IL-1RA组明显低于模型组(p<0.05),但仍高于假手术组(p<0.05);IL-1β+AG490组明显低于模型组(p<0.05),但仍高于假手术组(p<0.05);IL-1β组均显著高于模型组(p<0.05)。术后第14天,BBB评分模型组显著低于假手术组(p<0.01),IL-1RA组显著高于模型组(p<0.05),但仍低于假手术组(p<0.01);IL-1β组显著低于模型组(p<0.05)。结论 IL-1β可通过JAK2-STAT3促进脊髓损伤后胶质瘢痕形成,抑制IL-1β或JAK2-STAT3可减弱胶质瘢痕形成,促进脊髓神经功能恢复。

关键词: 关键词: 脊髓损伤, IL-1β, JAK2-STAT3, GFAP, vimentin

Abstract: Objective To investigate the mechanism of IL-1β in promotingglial scar formation after spinal cord injury. Methods The experimental model of SCI was created by extradural compression of the spinal cord using an aneurysm clip. Rats were randomly divided into model group, sham operation group, IL-1β inhibitor IL-1RA group, IL-1β group and IL-1β+JAK2-STAT3 inhibitor AG490 group, according to different interventions, then were given normal saline, IL-1RA, IL-1β and IL-1β+AG490 every 10μL respectively, sham group received only laminectomy. The motion function of the hindlimbs of rats was measured by Basso Beattie Bresnahan(BBB) scores and the expression of GFAP , vimentin and P-STAT3 were detected by Western blot technique, immunofluorescence assay and immunohistochemistry technique at corresponding time points(at the 8th , 12th hour, 1st, 3rd, 7th and 14th day after SCI). Results The expression trend of P-STAT3(at the 8th and 12th hour after SCI), GFAP and vimentin(at the 7th and 14th day afterSCI)was: the expressions of P-STAT3, GFAP and vimentin in the model group were significantly higher compared with the sham group(p<0.01), the expressions of P-STAT3, GFAP and vimentin in the IL-1RA group were significantly lower compared with the model group(p<0.05) whereas significantly higher compared with the sham group(p<0.05); the expressions of P-STAT3, GFAP and vimentin in the IL-1β+AG490 group were significantly lower compared with the model group(p<0.05)whereas significantly higher compared with the sham group(p<0.05), the expressions of P-STAT3, GFAP and vimentin in the IL-1β group weresignificantly higher compared with the model group(p<0.05). Conclusions IL-1β can improve glial scar formation via JAK2-STAT3 signal, inhibition of IL-1β or JAK2-STAT3 can reduce glial scar formation and promote functional recovery of spinal nerve.

Key words: Key words: spinal cord injury, IL-1β, JAK2-STAT3, GFAP, vimentin

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