阿魏酸钠通过Notch1/Hes信号通路对抗Aβ所致大鼠海马神经元损伤的机制研究  

Study on mechanism of sodium ferulate antagonizing Aβamyloid 1-42-induced rat hippocampal neuron damage by Notch1/Hes signaling pathway

作　　者：邹珊珊 闫恩志 ZOU Shanshan;YAN Enzhi(Teaching and Researching Section of Pharmacology,College of Basic Medicine,Jinzhou Medical University,Jinzhou,Liaoning 121001,China;Department of Pharmaceutical Supply,Affiliated Hospital of Chifeng College,Chifeng,Inner Mengolia 024005,China)

机构地区：[1]锦州医科大学基础医学院药理学教研室,辽宁锦州121001 [2]赤峰学院附属医院药品供应科,内蒙古赤峰024005

出　　处：《重庆医学》2023年第13期1943-1948,共6页Chongqing medicine

基　　金：国家自然科学基金项目(81400875);辽宁省科技厅计划项目(2019-ZD-0823);锦州科学技术计划项目(JZ2022B040)。

摘　　要：目的研究阿魏酸钠(SF)对β淀粉样蛋白1-42(Aβ_(1-42))所致大鼠海马神经元损伤的保护作用,并阐明其相关机制。方法将SD大鼠40只随机分为对照组、Aβ_(1-42)模型组、SF治疗组和SF+Notch1信号通路阻断剂(DAPT)组,每组10只。SF治疗组连续灌胃给药3周(100 mg/kg),对照组、Aβ_(1-42)模型组灌胃等量蒸馏水,SF+DAPT组连续腹腔注射DAPT(100 mg/kg)7 d,采用脑室内注射Aβ_(1-42)(5μL,2 mmol/L)制备痴呆动物模型,对照组注射等量生理盐水,脑室注射后第2天进行Morris水迷宫实验,检测大鼠的学习记忆能力,采用Nissl染色观察海马CA1区锥体神经元损伤情况,免疫组织化学染色观察胶质纤维酸蛋白(GFAP)表达水平,Western blot检测海马CA1区Notch1、NICD、Hes1蛋白表达。结果与对照组比较,Aβ_(1-42)模型组大鼠出现明显的空间学习记忆障碍,表现为逃避潜伏期较对照组明显延长,在原平台象限游泳时间占总时间百分比明显降低,同时伴有海马CA1区尼氏体碎裂,锥体神经元数目明显减少,差异均有统计学意义(P<0.05);GFAP免疫阳性细胞数明显增多,染色增强,胞体增大,突起增多并延长。Notch1、NICD、Hes1蛋白表达明显下降,差异均有统计学意义(P<0.05)。与Aβ_(1-42)模型组比较,SF给药3周能明显改善大鼠的学习记忆障碍,并减轻Aβ所致的上述神经细胞损伤及改变蛋白表达水平,DAPT可对抗SF对学习记忆的改善作用,下调NICD、Hes1蛋白表达,差异均有统计学意义(P<0.05),并部分对抗SF对海马神经元的保护作用及星形胶质细胞的激活。结论SF通过激活Notch1/Hes信号通路对抗Aβ_(1-42)所致大鼠海马神经元损伤及星形胶质细胞的活化。Objective To investigate the protective effect of sodium ferulate(SF)on Aβamyloid 1-42(Aβ_(1-42))-induced rat hippocampal neuron damage,and to clarify its relate mechanism.Methods Forty SD rats were randomly divided into the control group,Aβ_(1-42) model group,SF treatment group and SF+Notch1 signal pathway inhibitor(DAPT)group,10 cases in each group.The SF treatment group was given the medication(100 mg·kg^(-1)·d^(-1),intravenous injection)for 3 weeks continuous intragastric administration.The control group and Aβ_(1-42) model group were given the same amount of distilled water by gastric gavage.The SF+DAPT group was given DAPT(100 mg/kg)by continuous intraperitoneal injection for 7 d.The dementia animal model was prepared by the intracerebroventricular injection of Aβ_(1-42)(5μL,2 mmol/L).The control group was injected by the same amount of normal saline.The Morris water maze experiment was conducted to detect the rat learning and memory ability on the second day after cerebral ventricle injection.The Nissl staining was used to observe the injury of pyramidal neurons in hippocampal CA1 region.The immunohistochemical technique was used to observe the expression level of glial fibrillary acidic protein(GFAP).The expressions of Notch1,Notch1 intracellular domain(NICD),Hairyand enhancer of split 1(Hes1)protein were determined by the Western blot method.Results Compared with the control group,the Aβ_(1-42) model group appeared the significant the spatial learning and memory impairments,showing that the escape latency stage was significantly prolonged compared with the control group.The percentage of swimming time in the original platform quadrant accounting for the total time was decreased significantly,meanwhile this was accompanied by fragmentation of Nissellite in the CA1 region of hippocampus,the number of pyramidal neurons was decreased significantly,and the differences were statistically significant(P<0.05).The number of GFAP immunopositive cells was increased significantly,the staining was enhanced,t

关 键 词：阿魏酸钠 Β淀粉样蛋白 海马神经元 Notch1/Hes信号通路 

分 类 号：R742[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]