缺氧缺血性脑损伤新生大鼠磷酸化真核翻译起始因子2α和激活转录因子4表达的变化
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江苏省卫生厅科技计划重大项目基金资助(H200823)


Expression of phosphorylation of eukaryotic translation initiation factor 2α and activing transcription factor 4 in neonatal rats with hypoxic-ischemic brain damage
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    目的:了解新生大鼠缺氧缺血性脑损伤(HIBD)后磷酸化真核翻译起始因子2α[eIF2α(p)]-激活转录因子4(ATF4)表达的变化-方法:7日龄新生SD大鼠80只,随机分为2组:假手术组和HIBD组,每组各40只-HIBD组采用Rice方法建立新生大鼠HIBD模型,分别于缺氧缺血(HI)后6-12-24和72 h取其脑组织切片,采用免疫组织化学方法检测病变侧大脑皮质eIF2α(p)-ATF4蛋白的表达-假手术组不行缺氧缺血处理,采用同样方法检测其eIF2α(p)-ATF4蛋白的表达-结果:假手术组eIF2α(p)-ATF4蛋白少量表达,各时间点无明显变化(P > 0.05);HIBD组6 h可以观察到较多eIF2α(p)-ATF4蛋白,12 h达到高峰,72 h明显减少,但仍高于假手术组-HIBD组与假手术组比较,差异有统计学意义(P < 0.01)-HIBD组各时间点比较,差异有统计学意义(P < 0.01)-结论:eIF2α(p)-ATF4参与了新生大鼠HIBD病理生理过程-HIBD可能诱发了内质网应激反应,启动了PKR样内质网激酶(PERK)介导的未折叠蛋白应答(UPR)通路-

    Abstract:

    Objective: To study the changes of phosphorylated eukaryotic translation initiation factor 2α[eIF2α(p)]and expression of activing transcription factor 4(ATF4) in neonatal rats with hypoxic-ischemic brain damage(HIBD). Methods: Eighty 7-day-old Sprague-Dawley rats were randomly divided into 2 groups:sham operation group(n = 40) and HIBD group(n = 40). HIBD models were established by Rice method. At 6,12,24 and 72 h after hypoxia-ischemia (HI),the brain tissue of rats in HIBD group was obtained to prepare section. The changes of phosphorylation of eIF2α and expression of ATF4 in the lesion side cerebral cortex in rats were detected by immunohistochemical staining. The sham operation group was dealt with the same method without HI. Results: The expression level of eIF2α (p) and ATF4 increased at 6 h after HIBD,peaked at 12 h,decreased significantly at 72 h,but was still higher than that of sham operation group(P < 0.01). The differences in the expression level of eIF2α(p) and ATF4 in HIBD group among different time points were significant(P < 0.01). Conclusion: eIF2α(p) and ATF4 participate in the pathophysiological process of HIBD. HIBD may induce endoplasmic reticulum stress reaction,which initiate PKR-like endoplasmic reticulum kinase(PERK) mediated unfolded-protein response(UPR) signal pathway.

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潘 红,王 军,朱冠南,曹修丽,李 燕.缺氧缺血性脑损伤新生大鼠磷酸化真核翻译起始因子2α和激活转录因子4表达的变化[J].南京医科大学学报(自然科学版),2011,(11):1573-1577

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  • 收稿日期:2011-06-24
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