摘要
目的:观察苁蓉散对晚发型阿尔茨海默病(AD)模型小鼠认知障碍的影响,并探究其作用机制。方法:将50只ICR小鼠随机分为假手术组、晚发型AD模型组、苁蓉散低剂量组、苁蓉散高剂量组及氟他胺组,每组10只。除假手术组外,其余各组小鼠通过单侧睾丸切除和双侧海马齿状回Aβ_(1~42)注射建立晚发型AD动物模型。实验期间各组小鼠灌胃相应药物,假手术组和晚发型AD模型组小鼠均给予等体积生理盐水灌胃,1次/d,连续给药15 d。应用Morris水迷宫方法评价各组小鼠海马依赖的认知功能。HE染色法观察各组小鼠海马区形态学变化;ELISA法测定血清雄激素、促性腺激素释放激素(GnRH)水平。结果:晚发型AD模型组小鼠逃离潜伏期长于假手术组,小鼠穿越平台区次数及在第一象限游泳时间百分比低于假手术组,差异均有统计学意义(P<0.01);苁蓉散低、高剂量组小鼠逃离潜伏期短于晚发型AD模型组,苁蓉散高剂量组小鼠穿越平台区次数及在第一象限游泳时间百分比高于晚发型AD模型组,差异均有统计学意义(P<0.05或P<0.01);氟他胺组小鼠逃离潜伏期长于苁蓉散高剂量组,小鼠穿越平台区次数及在第一象限游泳时间百分比低于苁蓉散高剂量组,差异均有统计学意义(P<0.05)。假手术组小鼠海马齿状回(DG)区神经元(颗粒细胞)结构形态正常;晚发型AD模型组小鼠DG区颗粒细胞层断裂,大量神经元丢失;苁蓉散低、高剂量组小鼠DG区可见颗粒细胞层断裂程度减轻,且呈剂量依赖性;氟他胺组小鼠DG区颗粒细胞层损伤程度重于苁蓉散高剂量组。晚发型AD模型组小鼠DG区颗粒细胞层损伤面积大于假手术组(P<0.01);苁蓉散低、高剂量组DG区颗粒细胞层损伤面积小于晚发型AD模型组(P<0.01);氟他胺组小鼠DG区颗粒细胞层损伤面积明显大于苁蓉散高剂量组(P<0.01)。晚发型AD模型组小鼠血清雄激素、GnRH水平低于假手术组(P
Objective:To observe the effect of Congrong san on cognitive impairment in mice with late-onset Alzheimer's disease(AD)models and to investigate the mechanism of its effect.Methods:Totally 50 ICR mice were randomly divided into sham-operated group,late-onset AD model group,Congrong san low-dose group,Congrong san high-dose group and flutamide group,with 10 mice in each group.Except for the sham-operated group,the animal model of late-onset AD was established by unilateral gonadectomy(orchiectomy)and bilateral hippocampal dentate gyrus Aβ_(1-42) injection in each group.During the experiment,mice in each group were gavaged with the corresponding drugs.Mice in both sham-operated group and late-onset AD model groups were given equal volume of equal saline by gavage once a day for 15 days.The Morris water maze method was applied to evaluate the hippocampal-dependent cognitive function.After behavioral experiments,morphological changes in the hippocampal region were observed by HE staining in each group.Serum androgen and gonadotropin-releasing hormone(GnRH)concentrations were measured by ELISA method.Results:The latency to escape from the water was longer in the late-onset AD model group than in the sham-operated group,and the number of times the mice crossed the platform area and the percentage of time they swam in the first quadrant where the platform area was located were lower than those in the sham-operated group,with statistically significant difference(P<0.01).The escape latency of mice in the Congrong san low and high dose groups was shorter than that of the late-onset AD model group,and the number of crossing the plateau area and the percentage of swimming time in the first quadrant where the plateau area was located in the Congrong san high dose group was higher than that of the late-onset AD model group,and the differences were all statistically significant(P<0.05 or P<0.01).The escape latency in the flutamide group was longer than that of mice in the Congrong san high dose group,and the number of times th
作者
刘鹏飞
李炎
LIU Pengfei;LI Yan(Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases,Medical College of Yangzhou University,Yangzhou Jiangsu 225009,China;Affiliated Hospital of Yangzhou University,Yangzhou Jiangsu,225009,China)
出处
《中医药导报》
2023年第10期1-5,11,共6页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金青年项目(82104724)
扬州市重点研发项目(社会发展)(YZ2020092)
扬州大学科技创新培育基金项目(2019CXJ171)
扬州大学研究生科研与实践创新计划项目(SJCX21_1661)。
