Ca^(2+)对新生大鼠脑缺氧缺血后CREB磷酸化及神经元凋亡的影响  

Influence of Ca^(2+) on the phosphorylation of CREB, and the relationship between P-CREB and apoptotic neurons in neonatal rats after hypoxic-ischemia

作　　者：李文联[1] 王玲[1] 张红爱[1] 

机构地区：[1]第四军医大学唐都医院儿科,陕西西安710038

出　　处：《第四军医大学学报》2004年第3期217-219,共3页Journal of the Fourth Military Medical University

摘　　要：目的 :探讨Ca2 + 对新生大鼠脑缺氧缺血 (HI)后c AMP反应元件结合蛋白 (CREB)磷酸化及神经元凋亡的影响 ,为临床治疗缺氧缺血性脑损伤 (HIBD)提供理论依据 .方法 :7d龄SD鼠 (n =1 2 6 ) ,完全随机分为 3组 :假手术组 4 2只 (仅作颈正中切口 ,游离右颈总动脉不结扎 ) ;缺氧缺血组 4 2只、Ca2 + 拮抗剂加缺氧缺血组 (干预组 ) 4 2只 .后两组用 0号线结扎右颈总动脉 2h ,予以低氧 2h ,制备成缺氧缺血 (HI)脑损伤模型 .干预组动物分别在模型制成前、后腹腔内注射Ca2 + 拮抗剂尼莫地平 .用免疫组化法观察各组HI后不同时间点右侧海马CA1 区P CREB阳性细胞数 ;用TURNEL法观察各组HI后不同时间点右侧海马CA1 区凋亡细胞数 .结果 :HI组右侧海马CA1 区P CREB表达增强 (P <0 .0 1 ) ,4h达高峰后逐渐下降 ;HI组的凋亡细胞数增多 ,4 8h达高峰后逐渐下降 .干预组右侧海马CA1 区P CREB的表达较HI组无明显减少(P >0 .0 5 ) ,但凋亡细胞数较HI组明显减少 (P <0 .0 1 ) .结论 :Ca2 + 对CREB磷酸化无明显影响 ;Ca2 + 参与HI后神经元损伤 ;Ca2 + 拮抗剂可减轻神经元损伤 .AIM: To explore the influence of Ca 2+ on the phosphorylation of CREB and apoptosis of neurons in the neonatal rats brain after hypoxic ischemia (HI) so as to offer some theoretical basis for the therapy of HIBD in clinic. METHODS: Seven days old SD rats ( n =126) were randomly divided into three groups: the sham control group; the HI group; the Ca 2+ antagonist+HI group (intervention group). In the HI group and the intervention groups, the right common carotid artery was temporarily occluded for 2 h by No. 0 thread, then exposed to 80 mL/L oxygen and 920 mL/L nitrogen gas mixture for 2 h. In the intervention group, Nimodinpine was injected into the abdominal cavity before and after HI respectively. At different periods after HI, the expression of P CREB in different groups was detected by immunohistochemical methods. The apoptotic neurons in different groups was detected by Turnel method. RESULTS: In the HI group, the expression of P CREB in the right hippocampus was much higher than that in the sham control group ( P <0.01), and peaked 4 h after HI, and then continued to decrease. The number of apoptotic neurons in the right hippocampus was much higher than that in the sham control group ( P <0.01), and pesked 48 h after HI, and then continued to decrease. In the intervention group, the expression of P CREB has no difference with that in HI group ( P >0.05). But the number of apoptotic neurons was much fewer than that in HI group ( P < 0.01) . CONCLUSION: Ca 2+ has no obvious influence on the phosphorylation of CREB; Ca 2+ is involved in the damage of neurons during the period of post HI. Ca 2+ antagonist(Nimodipine) can reduce this damage.

关 键 词：缺氧缺血性脑损伤 c-AMP反应元件结合蛋白 凋亡 新生鼠 CA^2+拮抗剂 尼莫地平 

分 类 号：R392.11[医药卫生—免疫学]