还少丹对阿尔茨海默病模型小鼠学习记忆障碍及p38MAPK/ERK1/2信号通路的影响  

Effects of Huanshaodan on learning and memory impairment and p38MAPK/ERK1/2 signaling pathway in Alzheimer's disease model mice

作　　者：殷正达 丛培玮[1] 赵丹玉[1] 任路[1] 王旭[1] Yin Zhengda;Cong Peiwei;Zhao Danyu;Ren Lu;Wang Xu(College of Integrated Traditional Chinese and Western Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学中西医结合学院,沈阳110847

出　　处：《中华行为医学与脑科学杂志》2025年第2期104-110,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金(82274665);辽宁省教育厅面上项目(JYTMS20231831);辽宁中医药大学重点项目(2021LZY033)。

摘　　要：目的探究还少丹改善阿尔茨海默病(AD)快速老化模型SAMP8小鼠学习记忆障碍的效果,以及p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节激酶1/2(ERK1/2)介导的神经炎性反应机制。方法将7月龄SPF级的SAMP8雄性小鼠按随机数字表法分为3组(每组n=6):模型组、还少丹低剂量组(1.17 g/kg,2次/d,灌胃)和还少丹高剂量组(2.34 g/kg,2次/d,灌胃),6只同月龄的体质量相匹配的对抗快速老化SAMR1小鼠被设置为正常对照组,对照组和模型组给予等体积0.9%氯化钠溶液灌胃(2次/d)。全部小鼠接受了为期28 d的连续干预。采用Morris水迷宫评估小鼠的学习和记忆能力,通过免疫荧光染色来检测小鼠海马中星形胶质细胞标志物胶质纤维酸性蛋白(GFAP)和小胶质细胞标志物钙结合接头分子-1(Iba1)蛋白表达;采用ELISA法检测小鼠海马组织促炎因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的表达;采用Western blot法检测海马组织中的诱导型一氧化氮合酶(iNOS)和环氧合酶-2(COX-2)以及ERK1/2和p38MAPK的磷酸化表达水平。采用SPSS 20.0软件进行统计分析,使用重复测量方差分析或单因素方差分析进行各组间比较。结果Morris水迷宫结果显示,4组小鼠的逃避潜伏期存在时间和组别的交互效应(F=3.787,P<0.05)。第5~6天还少丹低、高剂量组小鼠逃避潜伏期均低于模型组(均P<0.05);在第4~6天,还少丹高剂量组小鼠的逃避潜伏期均低于还少丹低剂量组(均P<0.05)。4组小鼠的目标象限的停留时间和穿越平台次数均差异有统计学意义(F=8.587,12.633,均P<0.05)。模型组目标象限的停留时间[(17.8±3.4)s]和穿越平台次数[(1.6±0.6)次]均短于对照组[(40.6±3.7)s,(4.6±0.6)次]和高剂量组[(31.8±4.0)s,(2.8±0.8)次](均P<0.05)。Western blot结果揭示,4组小鼠海马组织中iNOS、COX-2、p-p38MAPK/p38MAPK和p-ERK1/2/ERK1/2的表达均差异有统计学意义(F=207.516,10.627,Objective To investigate the effect of Huanshaodan on improving learning and memory impairment in a mouse model of Alzheimer's disease(AD)which was named with senescence accelerated mouse-prone 8(SAMP8),as well as the neuroinflammatory response mechanisms mediated by the p38 mitogen activated protein kinase(p38MAPK)and extracellular signal regulated protein kinase 1/2(ERK1/2)signaling pathways.MethodsSeven-month-old SPF grade male SAMP8 mice were randomly assigned into three groups(6 mice in each group)using a random number table:model group,low-dose Huanshaodan group(1.17g/kg,twice daily via gavage),and high-dose Huanshaodan group(2.34g/kg,twice daily via gavage).Weight-matched seven-month-old male mice with anti-rapid aging traits(senescence-accelerated mouse-resistant 1,SAMR1)were designated as the normal control group(n=6).The mice in control group and the model group received 0.9%NaCl via gavage twice daily.All mice underwent continuous interventions for 28 days.The learning and memory abilities were assessed by Morris water maze.Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptor molecule-1(Iba1)as markers for astrocytes and microglial cells in the hippocampus,respectively.ELISA was used to measure pro-inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in hippocampal tissue.Western blot was used for analyzing the expression levels of pro-inflammatory enzymes,inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2),as well as phosphorylated levels of ERK1/2 and p38MAPK in hippocampal tissue.Data were statistically analyzed using SPSS 20.0.The repeated measures analysis of variance or one-way analysis of variance was used for multi groups comparison.ResultsMorris water maze test results indicated interactions between time and group in the escape latencies of the four groups of mice(F=3.787,P<0.05).From the 5th to 6th day,the escape latencies of the low-and high-dose

关 键 词：还少丹 阿尔茨海默病 神经炎性反应 P38丝裂原激活蛋白激酶 细胞外信号调节激酶1/2 

分 类 号：R28[医药卫生—中药学]