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1 h后再灌注24 h,制备局灶性脑I/R模型。HPC组吸入8%O23 h,制备HPC模型;S组只分离血管不置入线栓。于再灌注24 h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。
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 for 1 h followed by 24-h reperfusion. In group HPC, 8% oxy- gen was inhaled for 3 b at 12 h before ischemia. No nylon suture was inserted in group S. Neurological deficits were assessed at the end of 24-h reperfusion. And then rats were decapitated. The expressions of growth arrest and DNA-damage-induc- ible gene 153 （GADD153） protein in ischemic penumbra cerebral cortex were determined by immunohistochemieal 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 GADD 153 protein was significantly up-regulat- ed, in group I/R and group HPC than those in group S. The neurological deficit score and apoptotic index were significantly lower, the GADD153 protein expression was signifieantly down-regulated, in group HPC than those in group I/R （all P 〈 0.05）. Conclusion Hypoxia pretreatment can reduee the focal cerebral I/R-induced neuronal apoptosis mediated by endo- plasmic reticulum stress, which may be related with the down-regulation of GADD 153 protein expression in cerebral cortex.
出处
《天津医药》
CAS
北大核心
2013年第10期999-1001,I0006,共4页
Tianjin Medical Journal
关键词
再灌注损伤
内质网
应激
大脑皮质
低氧预适应
repeffusion injury
endoplasmic reticulum
stress
cerebral cortex
hypoxia preconditioning
