新生鼠缺氧缺血再灌注后海马p-CREB c-fos表达的变化(英文)

Changes of p CREB and c fos Expression in the Hippocampus of Neonatal Rats after Hypoxic Ischemic and Reperfusion Brain Damage

摘要:

目的：探讨新生鼠脑缺氧缺血再灌注后的神经保护机制。方法：7d龄SD新生鼠7窝(每窝选用8只,共56只),随机分为假手术对照组、缺氧缺血脑损伤组。经弹性管穿线阻断右颈总动脉3h,低氧(8％O_2和92％N_2混合气)1h,制备HIBD模型。3h后剪开扎线予再灌注,彩色多普勒监测右侧颈总动脉血流。免疫组化检测磷酸化的CREB和c-fos在不同时间点(再灌注3h,6h,12h,24h,48h,72h和7d及假手术后24h)海马区的表达。Thionin染色观测神经元凋亡情况。结果：HIBD再灌注3h,24h新生鼠右侧海马p-CREB表达达高峰,7d后下降至假手术组水平;c-fos表达6h达高峰,24h稍降,48h又升高,7d后显著降低但仍高于对照组(P< 0.01)。Thionin染色发现:再灌注24h右侧海马CA1区已有明显的凋亡,但7d后神经元无明显丢失。结论：缺氧缺血再灌注后CREB磷酸化可能经信号转导调节c-fos的表达,这对保护损伤侧海马锥体神经元,尤其是敏感的CA1区神经元是非常重要的。[中国当代儿科杂志,2003,5(1):12—16]

Abstract:

OBJECTIVE: To explore the protective mechanism after hypoxic-ischemic and reperfusion damage of the brain. METHODS: Seven-day-old SD rats from seven broods (eight rats from each brood, n = 56) were randomly divided into the HIBD group and sham operation group. The HIBD model was established by temporarily occluding the right common carotid artery for 3 hours with a thread through an elastic tube, and then they were exposed to the gas mixture of 80 ml/L oxygen and 920 ml/L nitrogen for 1 h. After 3 hs, the common carotid artery was reperfused. The blood flow of the right common carotid artery was detected by the Color Doppler. The expressions of p-CREB and c-fos in the hippocampus at different reperfusion periods (3 hs, 6 hs, 24 hs, 48 hs, 72 hs and 7 days after reperfusion and 24 hs after sham operation) were detected by immunohistochemical methods. Thionin staining was used to observe the apoptosis of neurons. RESULTS: In the HIBD group, the expression of p-CREB in the right hippocampus peaked 3 hs and 24 hs after reperfusion, and then decreased to the level of the sham group on the seventh day. The expression of c-fos reached the peak 6 hs after reperfusion, and another peak appeared 48 hs after reperfusion. Seven days after reperfusion, the number of c-fos positive cells decreased, but they were still more than those in the sham operation group ( P <0.0l). Using Thionin staining, we found that the apoptosis of neurons in the CA1 region marked 24 hs after reperfusion. CONCLUSIONS: The persistent activation of CREB in the hippocampus regulates the expression of c-fos through signal transduction, and it is involved in the course of neurons' survival and repair during the period of post hypoxic-ischemia reperfusion. It is very important for the protection of pyramidal hippocampal neurons of the damaged side, especially of the sensitive CA1 region. [Chin J Contemp Pediatr, 2003, 5(1): 12 - 16]