摘要
目的:观察血管性痴呆大鼠海马组织中内质网相关蛋白的表达变化及丁苯酞对相关蛋白表达的影响。方法:将SD大鼠分为模型组和丁苯酞干预组,行水迷宫实验,取材后应用Western Blot法和RTPCR法检测各组间内质网相关蛋白的表达变化情况。结果:水迷宫实验中给予丁苯酞后,大鼠的逃避潜伏期明显缩短。Model组大鼠逃避潜伏期较Sham组大鼠明显延长,3~5 d时逃避潜伏期延长更加显著(P<0.05);给予不同剂量丁苯酞后大鼠表现出逃避潜伏期较Model组大鼠明显缩短(P<0.05),尤其以NBP120组缩短更加显著。Western Blot方法检测发现,与假手术组相比,模型组中内质网应激各指标均显著上调(P<0.05);除了NBP30组中GRP78的表达外,其他各治疗组中其余指标均有所下调(P<0.05);除了XPB1和elF2α蛋白外,NBP120组对内质网应激的各指标均有显著下调作用(P<0.05)。RT-PCR法检测发现,与模型组相比,除了CHOP和elF2α的mRNA水平外,NBP120组对内质网应激的其余各指标均有显著下调作用(P<0.01);CHOP和elF2α的mRNA水平在NBP30组显著升高(P<0.01);这2个指标的mRNA水平在NBP60组和模型组之间差异无统计学意义。结论:血管性痴呆模型大鼠海马组织细胞内的内质网应激活跃,内质网应激参与了血管性痴呆发生发展过程。丁苯酞通过调节内质网应激各指标的表达,发挥神经保护作用。
Objective:To observe the expression of endoplasmic reticulum related protein in hippocampus of VD model rats,determine whether endoplasmic reticulum stress(ERS)plays an important role in the progress of VD,and observe whether different doses of butylphthalide(NBP)has protective effect by regulating the expressions of markers related to ERS.Methods:Grouping and model preparation were carried out in accordance.A Morris water maze experiment was conducted after giving NBP intervention.Western Blot and real time-PCR assay were used for evaluating the expression of endoplasmic reticulum related protein after bilateral common carotid artery occlusion among sham group,model group and different doses of NBP-treated groups.Results:The escape latency of model group was significantly longer than the sham group and NBP-treated groups on day 2(P<0.05).Compared with the sham group,the escape latency of the model group was significantly longer on days 3~5(P<0.05).We detected the protein expression of endoplasmic reticulum related protein.Except for GRP78 in 30 mg·kg^(-1) NBP group,the expressions of other proteins in rats treated with NBP significantly decreased compared with the model group(P<0.05).NBP of 120 mg·kg^(-1) significantly down-regulated the expression of all the proteins except for XPB1 and elF2α(P<0.05).Except for proteins,we also detected the mRNA expression of endoplasmic reticulum related protein.The mRNA levels of CHOP and elF2αwere significantly increased in NBP30 group compared with the model group(P<0.01)and there was no significant difference between NBP60 group and the model group.Besides CHOP and elF2α,all the other markers were significantly decreased in NBP120 group compared with the model group(P<0.01).The NBP120 group exhibited the most significant differences among the treated groups except for caspase-12(equal in NBP120 and NBP60 groups)(P<0.01).Conclusion:The markers of ERS in hippocampal tissue were activated in the VD model rats.After giving NBP,the expressions of endoplasmic reticulum rela
作者
牛小莉
楚宝
谢小华
徐国栋
董晓莉
吕佩源
NIU Xiao-li;CHU Bao;XIE Xiao-hua;XU Guo-dong;DONG Xiao-li;LPei-yuan(Department of Neurology,Hebei General Hospital,Shijiazhuang 050012,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2021年第8期747-753,共7页
Chinese Journal of New Drugs
基金
2019年度河北省医学科学研究重点课题资助项目(20190009)
河北省“三三三人才工程”资助项目(A202001045)。
关键词
血管性痴呆
内质网应激
丁苯酞
vascular dementia
endoplasmic reticulum stress
DL-3-n-butylphthalide
