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作 者:王婷婷 魏欢 杨永丽 周贤 胡阳 WANG Tingting;WEI Huan;YANG Yongli;ZHOU Xian;HU Yang(Department of General Medicine,Yan’an Hospital of Kunming City,Kunming 650051,China;Department of Neurology,Yan’an Hospital of Kunming City,Kunming 650051,China)
机构地区:[1]昆明市延安医院全科医学科,云南昆明650051 [2]昆明市延安医院神经内科,云南昆明650051
出 处:《基础医学与临床》2024年第8期1094-1100,共7页Basic and Clinical Medicine
基 金:云南省科技厅昆明医科大学应用基础研究联合专项面上项目(202001AY070001-260,202201AY070001-188);昆明市卫生科技人才培养项目暨“千”工程后备人选(2019-03-07-003)。
摘 要:目的探寻三七皂苷Rg1(notoginsenoside Rg1)保护神经系统防治阿尔茨海默病(Alzheimer′s disease,AD)的作用机制。方法采用SD大鼠侧脑室注射β淀粉样蛋白1-42(Aβ1-42)构建AD大鼠模型,将大鼠随机分为3组(假手术组、模型组和三七皂苷Rg1治疗组)。治疗组同时使用三七皂苷Rg1灌胃治疗,假手术组使用等量0.9%氯化钠溶液进行灌胃。Morris水迷宫实验(MWM)用于检测大鼠学习和记忆行为能力,化学比色法试剂盒检测大脑皮质丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,免疫组织化学法检测大脑皮质中caspase-3蛋白含量,Western blot检测p38和p-p38蛋白表达水平。结果模型组比假手术组大鼠逃避潜伏期延长,在第Ⅲ象限的逗留时间减少,跨越平台次数减少;大脑MDA含量升高,SOD含量活性降低;caspase-3蛋白阳性神经元数增加;p38蛋白无显著变化,p-p38蛋白表达水平显著上调(P<0.05)。三七皂苷Rg1治疗后AD大鼠逃避潜伏期缩短,目标象限逗留的时间及跨越平台次数明显增加,大脑MDA含量降低,SOD活性增加;caspase-3蛋白阳性神经元数减少,p38蛋白磷酸化水平降低(P<0.05)。结论三七皂苷Rg1可显著改善AD模型大鼠的学习记忆能力,增加抗氧化能力,起到神经系统保护作用。Objective To explore the mechanism of notoginsenoside Rg1 in preventing and treating Alzheimer′s disease(AD).Methods Rat model of AD was established by injecting amyloid beta peptide 1-42(Aβ1-42)into the lateral ventricle of SD rats.Then the animals were randomly divided into three groups:sham-operated group,model group and Rg1 treatment group.The treatment group was treated with Rg1 gavage and the sham-operated group was treated with saline gavage.Learning and memory capacity of rats were examined by Morris water maze experiment(MWM).Moreover,the contents of MDA and SOD in cerebral cortex were detected by chemical colorimetry;immuno-histochemistry was used to detect caspase-3 protein in the cerebral cortex and Western blot was employed to detect the expression of p38 and p-p38 proteins.Results Compared with the sham-operated group,the model group had a prolonged escape latency,reduced stay time in the target quadrant and reduced frequency of leaping over platform;increased MDA and decreased SOD in cerebral cortex;increased caspase-3 protein-positive neurons.The difference of p38 expression was not statistically significant and the phosphorylation of p38 was upregulated(P<0.05).The rats in Rg1 treatment group had a shorter escape latency,increased stay time in quadrantⅢ,increased frequency of leaping over platform,decreased caspase-3 positive neurons and the phosphorylation level of p38,decreased MDA and increased SOD compared with the model group(P<0.05).Conclusions Rg1 significantly improves learning and memory capacities,increases antioxidant capacity and plays neuro-protective effect in AD rat model by inhibition of p38 activation.
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