钙离子对新生大鼠脑缺氧缺血后C-AMP反应元件结合蛋白磷酸化的影响

Influence of Ca^(2+) on the phosphorylation of C-AMP response element bindin in neonatal rats after hypoxic-ischemia

目的:探讨新生大鼠脑缺氧缺血(HI)后钙离子对c-AMP反应元件结合蛋白(CREB)磷酸化的影响,为临床治疗缺血缺氧性脑病和研制新药提供理论依据。方法:7d龄SD鼠(n=126),完全随机分为3组:假手术组42只(仅作颈正中切口,游离右颈总动脉不结扎);缺氧缺血组42只、钙离子拮抗剂加缺氧缺血组(干预组)42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、后腹腔内注射钙离子拮抗剂尼莫地平。用免疫组化法测各组HI后不同时间点右侧海马CA1区P-CREB阳性细胞数。结果:HI组右侧海马CA1区P-CREB表达较对照组明显增强(P<0.01),4h达高峰后逐渐下降;干预组新生大鼠右侧海马CA1区P-CREB表达较HI组无明显减少(P=0.452>0.05)。结论:钙离子对CREB磷酸化无明显影响。钙离子拮抗剂可用于缺氧缺血性脑病治疗。

AIM:To explore the influence of Ca2+ on the phosphorylation of C- AMP resp onse element bindin(CREB) in the neonatal rats brain after hypoxic- ischemia(HI ),so as to offer basis for the therapy of HI in clinic and the development of so me new drugs. METHODS:Seven- day- old SD rats(n=126) were randomly divided into three gro ups:the sham operation group(control group only neck median incision,free right common carotid artery no deligation,n=42), the HI group(n=42) and the Ca2+ an tagonist and HI group(intervention group,n=42).In the HI and the intervention g roups, the right common carotid artery were temporarily occluded for 2 hours by No.0 threads,then exposed to 80 mL/L oxygen and 920 mL/L nitrogen gas mixture fo r 2 hours to provide HI brain injury models. In the intervention group the Ca2+ antagonist Nimodipine was injected into rats abdominal cavity before and after provided models respectively. At different periods after HI, the number of P- CREB positive cells in right hippocampi CA1 area in different groups were detect ed by immunohistochemical method. RESULTS:In the HI group ,the expression of P- CREB in the right hippocampi w as much higher than the control group(P< 0.01), and peaked at 4 hours and then d ecreased gradually. In the intervention group:The expression of P- CREB in the right hippocampi had no obvious decreasing to HI group(P=0.452 >0.05 ). CONCLUSION:Ca2+ has no obvious influence on the phosphorylation of CREB;Ca2 + antagonist(Nimodipine) can reduce HI in brain.