天津医药

• 实验研究 •    

低氧预适应对大鼠脑缺血再灌注诱导内质网应激的影响

孙成亮1,吕国义2,赵志斌1   

  1. 1. 连云港市第一人民医院麻醉科
    2. 天津医科大学第二医院麻醉科
  • 收稿日期:2013-01-04 修回日期:2013-03-18 出版日期:2013-10-15 发布日期:2013-10-15
  • 通讯作者: 孙成亮

Effects of Hypoxia Preconditioning on Endoplasmic Reticulum Stress Induced by Cerebral Ischemia-Reperfusion in Rats

SUN Cheng liang1,Lü Guo yi2,ZHAO Zhi bin3   

  1. 1. he First People’s Hospital of Lianyungang City
    2. he Second Hospital of Tianjin Medical University
    3. The First People’s Hospital of Lianyungang City
  • Received:2013-01-04 Revised:2013-03-18 Published:2013-10-15 Online:2013-10-15
  • Contact: SUN Cheng liang

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摘要：

【摘要】 目的  探讨低氧预适应对大鼠脑缺血再灌注诱导内质网应激的影响。 方法  健康雄性SD大鼠36只，采用随机数字表法随机分为假手术（S）组、缺血再灌注（I/R）组和低氧预适应（HPC）组，每组12只。采用右侧大脑中动脉阻闭1h后再灌注24h，制备局灶性脑I/R模型。HPC组吸入8%O2 3h，制备HPC模型；S组只分离血管不置入线栓。于再灌注24h时，行神经功能缺陷评分后断头取脑，免疫组化染色测定缺血皮质周围生长停止和DNA损伤诱导基因153（GADD153）蛋白表达，TUNEL法检测并计算细胞凋亡指数。 结果  与S组比较，I/R组和HPC组神经功能缺陷评分和凋亡指数升高，GADD153蛋白表达上调；与I/R组比较，HPC组神经功能缺陷评分和凋亡指数降低，GADD153蛋白表达下调（均P＜0.05）。  结论  低氧预适应可通过抑制内质网应激介导的细胞凋亡途径，减轻大鼠局灶性脑缺血再灌注损伤，其机制可能与下调GADD153蛋白表达有关

关键词: 再灌注损伤, 内质网, 应激, 大脑皮质, 低氧预适应

Abstract:

[Abstract]   Objective  To investigate the effect of hypoxia preconditioning (HPC) on endoplasmic reticulum stress
induced by cerebral ischemia-reperfusion (I/R) in rats.  Methods   Thirty-six male SD rats were randomly divided into three groups equally with twelve rats each: sham operation group (group S), group I/R and group HPC. The rat model of focal cere?bral I/R was produced by occluding right middle cerebral artery for1h followed by24-h reperfusion. In group HPC,8% oxy?gen was inhaled for3h at12h before ischemia. No nylon suture was inserted in group S. Neurological deficits were assessed at the end of24-h reperfusion. And then rats were decapitated. The expressions of growth arrest and DNA-damage-inducible gene 153(GADD153) protein in ischemic penumbra cerebral cortex were determined by immunohistochemical staining.The apoptotic neurons were detected by TUNEL assay, and the apoptotic index was calculated.  Results   The neurological deficit score and apoptotic index were significantly higher, the expression of GADD153protein was significantly up-regulated, in group I/R and group HPC than those in group S. The neurological deficit score and apoptotic index were significantly lower, the GADD153protein expression was significantly down- regulated, in group HPC than those in group I/R (allP<0.05).   Conclusion   Hypoxia pretreatment can reduce the focal cerebral I/R-induced neuronal apoptosis mediated by endo?plasmic reticulum stress, which may be related with the down-regulation of GADD153protein expression in cerebral cortex.

Key words: reperfusion injury, endoplasmic reticulum, stress, cerebral cortex, hypoxia preconditioning