首页|银杏叶提取物对帕金森小鼠海马神经元树突棘的保护作用

银杏叶提取物对帕金森小鼠海马神经元树突棘的保护作用

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目的 观察帕金森病(Parkinson's disease,PD)模型小鼠海马角 1(hippocampal cornu ammonis 1,CA1)区锥体神经元树突棘密度的变化,同时探讨银杏叶提取物(ginkgo biloba extract,EGb)对PD小鼠行为学、中脑黑质多巴胺神经元损伤的保护作用及对海马CA1区锥体神经元树突棘密度的改善作用,以揭示PD学习、记忆等非运动症状的病理机制,同时为EGb等天然药物的神经保护作用和临床应用提供实验依据。方法 取雄性C57BL/6小鼠12只,随机分为生理盐水对照组(NC组,n=4)、1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)模型组(MPTP 组,n=4)和 EGb+MPTP 组(EGb 组,n=4)。采用MPTP腹腔注射建立PD模型,EGb组小鼠在造模的基础上同时施加EGb给药处理。通过游泳实验和悬挂实验观察小鼠行为学改变,免疫组织化学实验分析中脑黑质多巴胺神经元损伤情况,以此验证PD模型是否成功建立。采用高尔基染色方法观察海马CA1区锥体神经元树突棘密度变化,并进行统计分析。结果 第1天,NC组游泳实验测试中的得分为(3。000±0)分,悬挂实验测试中的得分为(2。917±0。083)分;MPTP组游泳实验测试中的得分为(1。375±0。226)分,悬挂实验实验测试中的得分为(0。958±0。361)分;在第1天MPTP即造成小鼠行为学障碍,差异有统计学意义(P<0。05)。EGb组游泳实验测试中的得分为(2。500±0。522)分,悬挂实验实验测试中的得分为(2。250±0。305)分,与MPTP组比较,EGb逆转了行为损伤,差异有统计学意义(P<0。05)。MPTP组酪氨酸羟化酶(tyrosine hydroxylase,TH)的平均光密度(average optical density,AOD)为(0。486±0。011),NC 组为(0。690±0。015),EGb组为(0。596±0。029);MPTP组CA1区神经元树突棘密度为(10。850±1。488)/10 μm,NC 组为(15。330±0。742)/10 μm,MPTP 组为(15。750±0。978)/10 μm;MPTP 还导致中脑黑质多巴胺神经元损伤和海马CA1区锥体神经元树突棘密度降低,差异有统计学意义(P<0。05),而EGb能够改善MPTP造成的DA神经元损伤和树突棘密度降低,差异有统计学意义(P<0。05)。结论 EGb对MPTP模型小鼠行为学、中脑黑质多巴胺神经元及海马CA1区锥体神经元树突棘损伤具有保护作用。
Protective Effect of Ginkgo Biloba Extract on Dendritic Spines of Hippocampal Neurons in Parkinson's Disease
Objective To observe the changes in dendritic spine density of pyramidal neurons in the hippocampal cornu ammonis 1(CA1)region of Parkinson's disease(PD)model mice,and explore the protective effect of ginkgo biloba extract(EGb)on behavioral and midbrain dopamine neuron damage in PD mice,as well as the improvement of dendritic spine density of pyramidal neurons in the hippocampal CA1 region,in order to reveal the pathological mechanisms of non motor symptoms such as learning and memory in PD,and provide experimental evidence for the neuroprotective effects and clinical applications of natural drugs such as EGb.Methods A total of 12 male C57BL/6 mice were randomly divided into normal saline control group(NC group,n=4),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)model group(MPTP group,n=4)and EGb+MPTP group(EGb group,n=4).PD model was established by intraperitoneal injection of MPTP.The EGb group mice were also treated with EGb on the basis of modeling.Behavioral experiments and immunohistochemical detection of dopamine neurons in the substantia nigra of the midbrain were used to identify the model.Golgi staining was executed to observe changes in dendritic spine density of pyramidal neurons in the hippocampal CA1 area.Simultaneously,statistical analysis was conducted.Results On day 1,the scores of the NC group were(3.000±0)points in swimming test and(2.917±0.083)points in suspension test.The score of MPTP group was(1.375±0.226)points in swimming test and(0.958±0.361)points in suspension test.MPTP caused behavioral disorders in mice on day 1,and the difference was statistically significant(P<0.05).The scores of EGb group were(2.500±0.522)points in swimming test and(2.250±0.305)points in suspension test.Compared with MPTP group,EGb reversed the behavioral impairment,and the difference was statistically significant(P<0.05).The average optical density(AOD)of tyrosine hydroxylase(TH)in MPTP group was(0.486±0.011),and that in NC group was(0.690±0.015).EGb group was(0.596±0.029).The density of dendritic spines in CA1 region was(10.850±1.488)/10 μm in MPTP group,(15.330±0.742)/10 μm in NC group,and(15.750±0.978)/10 μm in MPTP group.MPTP also caused the damage of dopamine neurons in the midbrain substantia nigra and decreased the density of dendritic spines of pyramidal neurons in hippocampal CA1 region,with statistical significance(P<0.05).EGb could improve the damage of DA neurons and decrease the density of dendritic spines caused by MPTP,the difference was statistically significant(P<0.05).Conclusion EGb has a protective effect on the behavior,midbrain dopamine neurons,and dendritic spine damage of hippocampal CA1 pyramidal neurons in MPTP model mice.

Parkinson's disease1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineginkgo biloba extractdendritic spineshippocampushippocampal cornu ammonis 1

吕一霖、关晶心、时子乔、刘萱、张玉梅

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沈阳医学院基础医学院,辽宁 沈阳 110034

帕金森病 1-甲基-4-苯基-1,2,3,6-四氢吡啶 银杏叶提取物 树突棘 海马 海马角1

辽宁省教育厅2021年度科学研究经费项目面上项目

LJKZ1147

2024

中国卫生标准管理
《中国卫生标准管理》杂志社

中国卫生标准管理

影响因子:1.374
ISSN:1674-9316
年,卷(期):2024.15(18)