摘要
目的探究尤瑞克林对急性脑梗死(ACI)大鼠ERK1/2通路、HO-1、p-GSK-3β蛋白水平表达的影响。方法SD大鼠随机分为5组,即假手术组、模型组、尤瑞克林组、尤瑞克林+SCH772984组和SCH772984组。使用改良Zea-Longa法建立ACI模型,假手术组只切开分离颈动脉。尤瑞克林组腹腔注射尤瑞克林,SCH772984组1 h腹腔注射ERK1/2抑制剂SCH772984。尤瑞克林+SCH772984组同时使用两种药物干预。在建模后3d进行分析。神经功能缺损评分法(mNSS)用于评估神经功能。TTC染色检测脑梗死体积。ELISA检测血清缓激肽(BK)和血管生长因子(VEGF)水平。Western blot检测ERK1/2通路、HO-1、p-GSK-3β蛋白水平。结果建模后大鼠mNSS评分和脑梗死体积显著升高(P<O.Ol),尤瑞克林组mNSS评分和脑梗死体积显著低于模型组(P<0.01),SCH772984组mNSS评分和脑梗死体积显著高于模型组(P <0.01),尤瑞克林+SCH772984组的mNSS评分和脑梗死体积显著低于尤瑞克林组(P<0.01)。建模后各组大鼠的ERK1/2,OH-1和p-GSK-3β蛋白有升高(P<O.Ol),而尤瑞克林组的ERK1/2、OH-1和p-GSK-3β蛋白显著高于模型组(P<O.Ol),SCH772984组的ERK1/2、OH-1和p-GSK-3β蛋白显著低于模型组(P<0.01),尤瑞克林+SCH772984组的ERK1/2、OH-1和p-GSK-3β蛋白表达水平显著低于尤瑞克林组(P<0.01)。结论尤瑞克林可能通过上调ERK1/2通路促进HO-l、p-GSK-3β蛋白水平,从而抑制脑细胞凋仁保护ACI大鼠脑损伤。
Objective To investigate the effect of ureklin on the expression of ERK1/2 pathway,HO-1 and p-GSK-3β protein levels in rats with acute cerebral infarction(ACI).Methods SD rats were randomly divided into 5 groups,namely sham operation group,model group,Ureklin group,Ureklin+SCH772984 group and SCH772984 group.The ACI model was established using the modified Zea-Longa method,and the sham operation group only cut the isolated carotid artery.Ureklin group was injected intraperitoneally with uricillin,The SCH772984 group was intraperitoneally injected with the ERK1/2 inhibitor SCH772984.The Ureklin+SCH772984 group used both drug interventions.The analysis was performed 3 days after modeling.The neurological deficit score(mNSS)was used to assess neurological function.TTC staining was used to detect cerebral infarct volume.ELISA was used to detect serum bradykinin(BK)and vascular growth factor(VEGF)levels.Western blot was used to detect ERK1/2 pathway,H0-1,and p-GSK-3β protein levels.Results After modeling,the rat mNSS score and cerebral infarction volume were significantly increased(P<0.01).The mNSS score and cerebral infarction volume in the Ureklin group were significantly lower than those in the model group(P<0.01).The mNSS score and cerebral infarction volume in the SCH772984 group were significantly higher than those in the model group(P<0.01).The mNSS score and cerebral infarction volume in the ureklin+SCH772984 group were significantly lower than those in the ureklin group(P V 0.01).After modeling,the ERK1/2,OH-1 and p-GSK-3β proteins were increased in each group(P<0.01).The ERK1/2,OH-1 and p-GSK-3β proteins in the Ureklin group were significantly higher than those in the model group(P<0.01).The ERK1/2,OH-1 and p-GSK-3β proteins in the SCH772984 group were significantly lower than the model group(P<0.01).The expression levels of ERK1/2,OH-1 and p-GSK-3β in the ureklin+SCH772984 group were significantly lower than those in the Ureklin group(P<0.01).Conclusion Ureklin may promote the apoptosis of brain cells and up-regulate brain damage in ACI rats by up-regulating the ERK1/2 pathway to promote HO-1 and p-GSK-3 P protein levels.
作者
华立波
孙兴成
袁伟峰
王美堂
Hua Libo;Sun Xingcheng;Yuan Weifeng;Wang Meitang(Department of Emergency and Critical Service,Hospital of Changhai,Shanghai 200433,China)
出处
《脑与神经疾病杂志》
2019年第11期673-676,共4页
Journal of Brain and Nervous Diseases
