尼莫地平对邻苯二甲酸二丁酯所致小鼠学习记忆障碍的拮抗作用  

Antagonistic effect of nimodipine on DBP-induced learning and memory impairment in KM mice

作　　者：王龙[1] 葛剑[2] 陈谦学[1] 田道锋[1] 刘宝辉[1] 晏彪 WANG Long;GE Jian;CHEN Qian-xue;TIAN Dao-feng;LIU Bao-hui;YAN Biao(Dept of Neurosurgery,Renmin Hospital,Wuhan University,Wuhan 430060,China;Dept of Neurosurgery,Hospital of Hubei Province Armed Police Corps,Wuhan430061,China;College of Basic Medicine,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]武汉大学人民医院神经外科,湖北武汉430060 [2]武警湖北总队医院神经外科,湖北武汉430061 [3]湖北科技学院基础医学院,湖北咸宁437100

出　　处：《中国药理学通报》2019年第7期929-934,共6页Chinese Pharmacological Bulletin

基　　金：湖北科技学院校内培育科研项目(No 2019-20X017)

摘　　要：目的探究尼莫地平(Nim)对邻苯二甲酸二丁酯(DBP)所致KM小鼠学习记忆障碍的拮抗作用。方法 36只♂KM小鼠随机分成4组:对照组、50 mg·kg-1DBP组、2mg·kg-1Nim组及DBP+Nim组,实验周期28 d后,检测各组小鼠潜伏期,脑海马的钙调蛋白(Ca M)、钙/钙调素依赖性蛋白激酶II(Ca MKII)、蛋白激酶C(PKC)、细胞色素C(Cyt C)、caspase-3、ERK1/2、p-ERK1/2水平,并通过观察HE、Nissl染色及TUNEL检测脑海马CA1区病理学变化。结果与50 mg·kg-1DBP组比较,DBP+Nim组小鼠学习记忆能力有所改善,海马组织CA1病理学损伤及凋亡程度降低,PKC、Cyt C、caspase-3水平及p-ERK1/2表达量降低,Ca M、Ca MKII水平上升,差异均有统计学意义(P <0. 05)。结论DBP可影响Ca2+相关蛋白、上调p-ERK1/2表达,诱导KM小鼠脑海马神经元损伤及凋亡,而Nim改善DBP所致小鼠的学习记忆障碍,可能与其可拮抗胞内Ca2+浓度增加,降低DBP暴露后小鼠脑组织p-ERK1/2及caspase-3水平有关。Aim To explore the antagonistic effect of nimodipine (Nim) on dibutyl phthalate (DBP)- induced learning and memory impairment in KM mice. Methods Thirty-six male KM mice were treated with saline (control), 50 mg·kg -1 DBP, 2 mg·kg -1 Nim, and DBP+Nim lasted for 28 days. The latency of KM mice in each group was measured. Levels of calmodulin (CaM), calmodulin/calmodulin-dependent protein kinase II (CaMKII), protein kinase C (PKC), cytochrome C (Cyt C) and caspase-3 in hippocampus of KM mice in each group were detected. And expressions of ERK1/2 and p-ERK1/2 were evaluated. In addition, the pathological changes of hippocampal CA1 region were also analyzed by HE, Nissl staining, and TUNEL assay. Results Compared with 50 mg·kg -1 DBP group, the learning and memory impairment of KM mice in DBP+Nim group was alleviated, the pathological damage and apoptosis in CA1 region of hippocampus were reduced, the levels of PKC, Cyt C, caspase-3 and p-ERK1/2 decreased, while the levels of CaM and CaMKII increased accordingly ( P <0.05). Conclusions DBP affects Ca 2+-related proteins and up-regulates p-ERK1/2 expression, inducing hippocampal neuronal damage and apoptosis, whereas Nim can improve DBP-induced learning and memory impairment in KM mice, which may be related to the ability of Nim to reduce the levels of p-ERK1/2 and caspase-3 in brain tissues of mice after DBP exposure by blocking DBP-induced Ca 2+ concentration.

关 键 词：尼莫地平 邻苯二甲酸二丁酯 海马神经元 钙离子 细胞外调节蛋白激酶 细胞凋亡 

分 类 号：R-332[医药卫生] R322.81