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雷公藤内酯醇(T10)通过抑制脊髓内胶质细胞的激活改善大鼠CFA诱导的炎性痛的机制研究
  • ISSN号:1000-7547
  • 期刊名称:神经解剖学杂志
  • 时间:2014.11.15
  • 页码:621-628
  • 分类:Q421[生物学—神经生物学;生物学—生理学]
  • 作者机构:[1]第四军医大学学员旅,西安710032, [2]第四军医大学人体解剖与组织胚胎学教研室暨梁銶琚脑研究中心,西安710032, [3]南京军区南京总医院麻醉科,南京210018
  • 相关基金:国家自然科学基金(81371238)
  • 相关项目:脊髓背角DNA甲基化介导NR2B基因表达上调参与疼痛慢性化的机制研究
中文摘要:

目的:观察腹腔注射雷公藤内酯醇(Triptolide,T10)对完全弗氏佐剂(complete Freund’s adjuvant,CFA)诱导的大鼠慢性炎性痛行为的改善作用并探讨其机制。方法:SD大鼠随机分为四组,即Saline+Veh组、Saline+T10组、CFA+Veh组和CFA+T10组。后两组大鼠于右侧足底注射CFA制备大鼠慢性炎性痛模型,前两组则在相同部位注射生理盐水。第二组和第四组大鼠分别于造模前1 h给予T10腹腔注射,随后每12 h给予腹腔注射药物1次,持续用药7 d;第一组和第三组则以相同方式给予100 ml/kg的生理盐水作为对照。采用辐射热法和机械刺激法连续观察给药后大鼠的痛行为;应用免疫组织化学染色和Western Blot方法观察连续给予T10 3d和7 d后大鼠腰膨大平面脊髓背角内小胶质细胞和星形胶质细胞的活化程度;应用实时定量PCR(RT-PCR)方法观察连续给药7 d后大鼠腰5背根神经节内炎性因子,如白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1 beta,IL-1β)和肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)的表达变化。结果:(1)与CFA+Veh组相比,CFA+T10组大鼠机械缩足阈值及辐射热痛潜伏期显著下降(P〈0.05),并持续到造模成功后7 d,表明腹腔注射T10可以明显改善CFA诱导的大鼠机械痛敏和辐射热痛敏。(2)免疫组织化学染色和Western Blot结果显示:造模后3 d和7 d后CFA+Veh组大鼠脊髓背角出现大量CFA诱导活化的小胶质细胞和星形胶质细胞;小胶质细胞标记物IBa-1和星形胶质细胞标记物GFAP的表达量分别在CFA造模后3 d和7 d显著增高(P〈0.05),而给予T10 3 d和7 d后炎性痛大鼠腰膨大平面IBa-1和GFAP的活化程度均显著减轻(P〈0.05)。(3)RT-PCR结果显示:与Saline+Veh组相比,CFA造模7 d后腰5背根神经节内炎性因子IL-1β、IL-6 mRNA和TNF-αmRNA的表达显著增高(P〈0.05),腹腔注射T10 7 d后上述炎性因子的?

英文摘要:

Objective:To observe the improvement and potential mechanism of intraperitoneal injection of tripterygium wilfordii hook F( T10) on complete Freund's adjuvant( CFA)-induced chronic inflammatory pain behavior in rats.Methods:SD rats were divided into 4 groups randomly,Saline + Veh group,Saline + T10 group,CFA + Veh group and CFA + T10 group,and 6 rats in each group.For the last two groups,CFA was injected into the right hindpaw to establish the inflammatory pain model;while the normal saline was injected into the same regions in first two groups.For the second and forth group rats,T10 was injected intraperitoneally 1 h before the injection of CFA and each 12 h after the iniection of CFA for 7 d.At the same time,a same dose of saline instead of T10 was used in the first and third group rats as control groups.Radiant heat and mechanical stimulation methods were applied to investigate the of pain behavior continually.Immunohistochemical staining and Western Blot were used to qualitatively and semi-quantitatively analyze the microglia and astrocyte activation in spinal cord dorsal horn after intraperitoneal injection of T10 on 3 d and 7 d.Real-time PCR( RT-PCR) was applied to qualitatively analyze the inflammation factors,such as interleukin-6( IL-6),interleukin-1 beta( IL-1β),tumor necrosis factor-alpha( TNF-α) in lumbar 5 ganglia after a 7 d consecutive intraperitoneal injection of T10.Results:( 1) Compared with CFA + Veh group,mechanical withdraw threshold and the thermal withdraw latency showed significant decrease in CFA + T10 groups( P〈0.05),which also lasted until to the ends of the experiment on 7d,indicating intraperitoneal injection of T10 can significantly improve CFA induced mechanical and thermal hyperalgesia in rats.( 2) Immunohistochemical staining and Western Blot results showed that on 3 d and 7 d after CFA injection,large number of CFA induced activation of microglia and astrocyte were observed respectively at spinal dorsal horn in CFA +Ve

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期刊信息
  • 《神经解剖学杂志》
  • 中国科技核心期刊
  • 主管单位:第四军医大学
  • 主办单位:中国解剖学会
  • 主编:李云庆
  • 地址:西安第四军医大学基础医学部解剖学教研室转<神经解剖学杂志>编辑部
  • 邮编:710032
  • 邮箱:chinjna@fmmu.edu.cn
  • 电话:029-84772169
  • 国际标准刊号:ISSN:1000-7547
  • 国内统一刊号:ISSN:61-1061/R
  • 邮发代号:52-214
  • 获奖情况:
  • 获第二次全军医学期刊质量评比优秀期刊奖,1998年中国科技期刊影响因子排序第82名(1286种源...
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  • 被引量:5787