河北医科大学学报

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p38MAPK/MMP-9信号通路对新生大鼠脑缺氧缺血损伤的影响

  

  1. 1.河北医科大学第三医院麻醉科，河北 石家庄 050051；2.河北医科大学第二医院麻醉科，河北 石家庄 050000
  • 出版日期:2017-09-25 发布日期:2017-09-18
  • 作者简介:于沛霞（1979-），女，天津人，河北医科大学第三医院主治医师，医学硕士，从事临床麻醉学研究。
  • 基金资助:
    河北省医学科学研究重点课题（20130221）

The effects of P38MAPK/MMP9 signaling pathway on hypoxic ischemic brain damage in neonatal rats

  1. 1.Department of Anesthesiology， the Third Hospital of Hebei Medical University， Shijiazhuang
    050051， China； 2.Department of Anesthesiology， the Second Hospital of Hebei
    Medical University， Shijiazhuang 050000， China
  • Online:2017-09-25 Published:2017-09-18

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摘要： ［摘要］〓
〖HTH〗目的〖HTSS〗〖KG*2〗观察依达拉奉对新生大鼠脑缺氧缺血损伤(hypoxicischemic brain damage，HIBD)的影响，探讨依达拉奉可能通过p38MAPK/基质金属蛋白酶9（matrix metalloprotein9,MMP9）信号通路发挥脑保护作用。
〖HTH〗方法〖HTSS〗〖KG*2〗 Rice方法建立新生大鼠（7 d）HIBD模型，随机分为假手术组、HIBD组、依达拉奉组、吡啶咪唑类衍生物(SB203580)组，每组16只。采用五点量表法评估神经功能，并测定脑水含量。检测超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehyde，MDA）浓度。采用酶联免疫法检测MMP9浓度。采用Western blot法检测细胞外信号调节激酶(extracellular signalregulated kinase1/2，ERK1/2)、cJun氨基末端激酶（cJun Nterminal kinase 1/2，JNK1/2）、p38MAPK浓度以及pERK1/2、pJNK1/2和pp38MAPK浓度。
〖HTH〗结果〖HTSS〗〖KG*2〗HIBD组、依达拉奉组、SB203580组神经功能评分和脑含水量明显高于假手术组，SOD活性低于假手术组，MDA含量和MMP9浓度高于假手术组，依达拉奉组和SB203580组神经功能评分和脑含水量明显低于HIBD组，SOD活性高于HIBD组，MDA含量和MMP9浓度低于HIBD组（P＜005）。 HIBD组JNK1/2、pJNK1/2、p38MAPK、pp38MAPK含量明显高于假手术组、依达拉奉组、SB203580组，ERK1/2、pERK1/2含量明显高于假手术组（P＜005）。
〖HTH〗结论〖HTSS〗〖KG*2〗依达拉奉对新生大鼠（7 d）HIBD的神经保护作用与其抑制促炎介体的产生和下调JNK1/2和p38MAPK活化相关联。其可能与下调P38MAPK/MMP9通路活性有关。

关键词: 缺氧缺血, 脑, 依达拉奉, 大鼠

Abstract: ［Abstract］  Objective〖HTSS〗〓To observe the effect of edaravone on hypoxicischemic brain damage(HIBD) in neonatal rats and to investigate the protective effect of edaravone on brain through p38MAPK/matrix metalloprotein9（MMP9） signaling pathway.
〖HTH〗〖WTHZ〗Methods〖HTSS〗〓Neonatal rats were randomly assigned to the sham operation group, the HIBD group, the edaravone group, the SB203580 group(n=16, each group). The surgical procedure of HIBD was described previously. Ischemic penumbrae of the cerebral cortex were harvested to determine superoxide dismutase(SOD), malondialdehyde(MDA). Measurements of MMP9 in the brain samples were performed using ELISA. Measurements of extracellular signalregulated kinase1/2 （ERK1/2）, cJun Nterminal kinase 1/2 （JNK1/2）, p38MAPK, pERK1/2, pJNK1/2, and pp38MAPK concentration in the brain samples were performed using western blot analysis.
〖HTH〗〖WTHZ〗Results〖HTSS〗〓The neurological function score and cerebral water content of the HIBD group, edaravone group and SB203580 group were significantly higher than those in the sham operation group. The activity of SOD was lower than that in the sham operation group, and the content of MDA and MMP9 were higher than those of the sham operation group. The neurological function score and cerebral water content of edaravone group and SB203580 group were significantly lower than those in HIBD group. The activity of SOD was higher than that of the HIBD group, and the content of MDA and MMP9 were lower than those of the HIBD group（P＜005）. The contents of JNK1/2, pJNK1/2, p38MAPK and pp38MAPK in HIBD group were significantly higher than those in the sham operation group, edaravone group and SB203580 group, and the contents of ERK and pERK were significantly higher than those in the sham operation group(P＜005).
〖HTH〗〖WTHZ〗Conclusion〖HTSS〗〓The neuroprotective effect of edaravone on HIBD in neonatal rats (7 d) was associated with inhibition of proinflammatory mediator production and downregulation of JNK1/2 and p38MAPK activation, which may be related to down regulation of p38MAPK/MMP9 pathway activity.

Key words: hypoxiaischemia, brain, edaravone, rats

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