环磷腺苷葡甲胺对新生缺氧缺血性脑病猪心肌CREB含量的影响

The effect of meglumine cyclic adenylate on the expression of CREB in myocardial tissue of piglets with hypoxic-ischemic encephalopathy

目的新生猪缺氧缺血性脑病时环磷腺苷葡甲胺(MCA)对心肌组织环磷酸腺苷反应元件结合蛋白(CREB)表达的影响。方法选生后3-7天的新生猪22头,随机分成假手术组(Sham)、缺氧缺血组(HIE)和环磷腺苷葡甲胺组(MCA)。Sham组4头猪,只游离双侧颈动脉;HIE组9头,阻断双侧颈总动脉同时控制呼吸吸人6%氧气;MCA组9头,在缺血缺氧前静脉注射环磷腺苷葡甲胺(2mg/kg)。每头新生猪在缺氧前和缺氧后10h,采用化学发光法测定肌钙蛋白I含量,电镜观察心肌细胞结构变化,western blot方法检测CREB蛋白的表达,Real-timePCR法检测CREB mRNA的表达水平。结果缺氧缺血10h,HIE组肌钙蛋白值显著高于Sham组或MCA组(P<0.01)。Sham组心肌细胞结构完好,HIE组心肌细胞损伤严重,MCA组心肌细胞结构只有轻微改变。心肌组织CREB的蛋白和mRNA表达水平HIE组明显低于sham组,而MCA组明显高于HIE组(P<0.01)。结论新生猪缺氧缺血性脑病时,MCA上调心肌组织CREB的表达。

Objective To investigate the effect of meglumine cyclic adenylate（MCA） on the expression of cAMP response element binding protein（CREB） in myocardial tissue of piglets with hypoxic-ischemic encephalopathy（HIE）.Methods 22 term piglets at 3 to 7 days after birth were subjected and divided into sham operation group（4）,HIE（9,block bilateral common carotid artery temporarily and give 6%oxygen mechanically） group and MCA（9,injection of MCA in vein before ischemia）group.The content of cardial troponin I in myocardium was measured by chemiluminescence,myocardial cell structure changes was observed by electron microscope,the expression of CREB protein and mRNA was detected by Western blot and Real-time PCR method respectively.Results The content of cardial troponin I in myocardium was significantly higher in HIE group than in sham group or MCA group 10 hours after hypoxia（P〈0.01）.The cellular structure of myocardium was intact in sham group,but injured severely in HIE group,milder in MCA group.Compared with,The expression levels of CREB protein and mRNA in myocardial tissue were decreased in HIE group than in sham group,but increased significantly in MCA group than in HIE group（P〈0.01）.Conclusion MCA could up-regulate the expression of CREB in myocardial tissue of neonatal piglets with hypoxic-ischemic encephalopathy.