蛛网膜下腔出血大鼠脑干组织叉头框蛋白的表达及尼莫地平的影响  

Study on the expression of FOXO in brain stem of rats with subarachnoid hemorrhage and effect of nimodipine on the expression

作　　者：吴冰[1,2] 康劲松[3] 王贺元[4] 晞欣[3] 邱海洋[3] 王伟伟[3] 罗祺[1] 

机构地区：[1]吉林大学白求恩第一医院神经外科,吉林长春130021 [2]吉林大学中日联谊医院神经外一科,吉林长春130033 [3]吉林大学白求恩医学院病理生理学教研室,吉林长春130021 [4]吉林大学白求恩第一医院内分泌科,吉林长春130021

出　　处：《中风与神经疾病杂志》2011年第5期402-406,共5页Journal of Apoplexy and Nervous Diseases

基　　金：吉林省科技发展计划项目-白求恩专项(200705120)

摘　　要：目的研究丝氨酸/苏氨酸蛋白激酶B[protein Kinase B,PKB(AKT)]、叉头框蛋白[forkhead box(FOXO),FKHR]在大鼠蛛网膜下腔出血脑血管痉挛动物模型中早期(1d)的表达、活化情况及应用尼莫地平的影响。方法将Wistar大鼠分为假手术组(对照组)、SAH模型组、SAH后给尼莫地平治疗组(治疗组)。经颅多普勒超声(TCD)检测大鼠基底动脉的最大血流速度(Maximum velocity of Basilar artery blood flow,Vmba)。脑干组织进行免疫组化染色。结果 SAH模型组与对照组相比基底动脉血流加快(P<0.05)。治疗组比SAH模型组基底动脉血流速度慢(P<0.05)。在对照组AKT、P-AKT(磷酸化-AKT)、FKHR、P-FKHR(磷酸化-FKHR)均可见阳性细胞表达。在SAH模型组:AKT表达增多,但与对照组比较差异无显著性(P>0.05);P-AKT表达减少,与对照组比较差异有显著性(P<0.05)。在治疗组AKT、P-AKT表达较对照组和SAH模型组均增加,差异具有显著性(P<0.05)。在SAH模型组FKHR表达增加,P-FKHR表达减少,与对照组比较差异有显著性(P<0.05);在治疗组FKHR表达较对照组和SAH模型组均减少,P-FKHR表达较对照组和SAH模型组均增加,差异具有显著性(P<0.05)。结论 PKB/AKT介导的磷酸化能够诱导FOXO蛋白从细胞核到细胞质的重新定位,诱导FOXO蛋白的活性发生改变,并参与了大鼠SAH后早期(1d)CVS的形成。尼莫地平具有缓解SAH后早期(1d)CVS的作用。Objective To study on the early（1d）expression,activation conditions and application of nimodipine effects on serine/threonine protein kinase（AKT）and forkhead box protein（FKHR）in the rat cerebral vasospasm following subarachnoid hemorrhage in animal models.Methods The Wistar rats were divided into sham-operation group（Called the control group）,SAH model group and SAH nimodipine treatment group（called the treatment group）.Transcranial Doppler ultrasound（TCD）was used to detect the largest rat basilar artery blood flow velocity（Vmba）.Brainstem organization was immunohistochemical stained.Results Compared with the control group,SAH model group showed faster basilar artery blood flow speed（P0.05）.The treatment group＇s basilar artery blood flow velocity was slower than in SAH model group（P0.05）.In the control group,AKT,P-AKT,FKHR,and P-FKHR-positive cells were seen.In the SAH modelgroup,AKT expression increased,but the difference had no significance compared with the control group（P0.05）.P-AKT expression was decreased,compared with the control group,and the difference was significant（P0.05）.In the treatment group,AKT and P-AKT expression were increased compared with the control group and the SAH model group,the difference was significant（P0.05）.FKHR expression increased in the SAH model group,P-FKHR expression was decreased,difference was significant compared with the control group（P0.05）.In the treatment group,FKHR expression were reduced compared with the control group and SAH model groups,P-FKHR expression were increased compared with the control group and the SAH model group,the difference was significant（P0.05）.Conclusion PKB/AKT-mediated phosphorylation can induce FOXO proteins from the nucleus to the cytoplasm of the re-positioning to induce the activity of FOXO proteins changed,and participated in the early stage after SAH in rats（1d）CVS formation.Ease effect of Nimodipine may be on early（1d）CVS after SAH.

关 键 词：蛛网膜下腔出血 大鼠 脑干 叉头框蛋白 尼莫地平 

分 类 号：R743.35[医药卫生—神经病学与精神病学]