摘要
目的探讨右美托咪定(DEX)调节MAPK/ERK-CREB通路对大鼠海马神经元凋亡的保护作用。方法通过腹腔注射氯化锂-毛果芸香碱构建癫痫持续状态(SE)大鼠模型,并随机分为4组,每组各10只。SE+DEX组在SE模型构建成功后腹腔注射DEX 1μmol/L,阳性对照组腹腔注射1μmol/L苯巴比妥,药物干预24 h后,通过Nissl法和TUNEL法检测大鼠海马神经元损伤及凋亡情况,Western blot法检测大鼠海马组织中MAPK、pERK、pCREB蛋白和凋亡相关蛋白caspase-3、Bcl-2、Bax表达。结果与正常对照组相比,SE、阳性对照组、SE+DEX组大鼠Racine分值显著增加(P<0.05),大鼠海马神经元数、Bcl-2蛋白表达量显著减少(P<0.05),棕褐色TUNEL阳性细胞数、MAPK、p-ERK、p-CREB、caspase-3、Bax、Bax/Bcl-2蛋白表达量显著增加(P<0.05)。与SE组相比,阳性对照组、SE+DEX组大鼠Racine分值显著降低(P<0.05),大鼠海马神经元数、Bcl-2蛋白表达量显著增加(P<0.05),棕褐色TUNEL阳性细胞、MAPK、p-ERK、p-CREB、caspase-3、Bax、Bax/Bcl-2蛋白表达量显著减少(P<0.05)。结论DEX可能通过抑制MAPK/ERK-CREB通路抑制海马神经元凋亡对其有保护作用。
Objective To investigate the protective effect of dexmedetomidine(DEX)on apoptosis of hippocampal neurons in rats with status epilepticus(SE)by regulating MAPK/ERK-CREB pathway.Methods SE rat model was established by intraperitoneal injection of lithium pilocarpine,and was randomly divided into 4 groups,with 10 rats in each group.1μmol/L of DEX was injected intraperitoneally in the SE+DEX group and 1μmol/L of phenobarbital was injected intraperitoneally in the positive control group,after 24 hours of drug intervention,Nissl and TUNEL methods were used to detect the damage and apoptosis of hippocampal neurons,and Western blot was used to detect the expression of MAPK,p-ERK,p-CREB and caspase-3,Bcl-2,Bax in hippocampus of rats.Results Compared with the control group,the Racine scores of SE group,positive control group and SE+DEX group were significantly higher(P<0.05),the number of hippocampal neurons and the expression of Bcl-2 protein expressions were decreased significantly(P<0.05),and the number of sepia TUNEL positive cells,MAPK,p-ERK,p-CREB,caspase-3,Bax,Bax/Bcl-2 protein levels increased significantly(P<0.05).Compared with the SE group,the Racine scores of the positive control group and the SE+DEX group were significantly lower(P<0.05),the number of hippocampal neurons and the expression of Bcl-2 protein were significantly increased(P<0.05),and the number of sepia TUNEL positive cells,MAPK,p-ERK,p-CREB,caspase-3,Bax,Bax/Bcl-2 protein expressions decreased significantly(P<0.05).Conclusions DEX may inhibit apoptosis of hippocampal neurons by inhibiting MAPK/ERK-CREB pathway,and then improve epilepsy in rats.
作者
朱建坡
梁冰
ZHU Jianpo;LIANG Bing(The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China)
出处
《中风与神经疾病杂志》
CAS
2020年第4期317-321,共5页
Journal of Apoplexy and Nervous Diseases
基金
2018年度河南省自然科学基金(医学科技攻关计划类)(182300410386)。
