摘要
目的探讨槲皮素调控Wnt信号通路对阿尔茨海默病(AD)模型小鼠海马神经的影响。方法选取SPF级6周龄小鼠60只,随机分为假手术组、模型组及实验组,每组20只。模型组和实验组小鼠双侧海马区注射Aβ25-35建立小鼠AD模型,实验组小鼠灌胃槲皮素(50 mg·kg^(-1)·d^(-1)),假手术组、模型组小鼠灌胃等体积生理盐水,连续干预14 d。采用Y-迷宫法检测小鼠学习记忆水平,TUNEL法检测小鼠海马组织凋亡情况,免疫组化法检测小鼠海马组织轴蛋白(Axin)和β连环蛋白(β-catenin)表达情况,蛋白质免疫印迹法(Western blot)检测小鼠海马组织Axin、β-catenin和Wnt 1蛋白表达量,酶联免疫吸附试验(ELISA)检测小鼠血清丝氨酸苏氨酸类激酶(GSK-3β)和蛋白磷酸酶2A(PP2A)含量。结果自Y-迷宫训练的第2天开始,实验组小鼠的错误次数明显低于模型组(P<0.01);模型组小鼠海马组织凋亡率、Axin蛋白表达、GSK-3β水平均明显高于假手术组(P<0.01),而β-catenin蛋白表达、Wnt 1蛋白表达、PP2A活性均明显低于假手术组(P<0.01);实验组小鼠海马组织凋亡率、Axin蛋白表达、GSK-3β活性均明显低于模型组(P<0.01),而β-catenin蛋白表达、Wnt 1蛋白表达、PP2A水平均明显高于模型组(P<0.01)。结论槲皮素可以通过降低海马组织凋亡率减轻AD小鼠海马组织神经损伤,可能与调节Wnt信号通路有关。
Objective To explore the effects of quercetin on hippocampal nerves in the model mice with Alzheimer’s disease(AD)by regulating Wnt signaling pathway.Methods Sixty SPF-level 6-week-old mice were enrolled and randomly divided into sham operation group,model group and experimental group,with 20 cases in each group.In model group and experimental group,mice were injected with Aβ25-35 at bilateral hippocampus to establish AD mice models.The experimental group was administered intragastrically with quercetin(50 mg·kg^(-1)·d^(-1)),while sham operation group and model group were administered intragastrically with the same volume of normal saline.They were continuously intervened for 14 d.The levels of learning and memory were detected by Y-maze test.The apoptosis of hippocampal tissues was detected by TUNEL.The expressions of Axin andβ-catenin in hippocampal tissues were detected by immunohistochemistry.The expressions of Axin,β-catenin and Wnt 1 were detected by Western blotting.The contents of serum glycogen synthesis kinanse 3β(GSK-3β)and protein phosphatase 2A(PP2A)were detected by enzyme-linked immunosorbent assay(ELISA).Results From the second day after Y-maze test on,times of errors in experimental group were significantly fewer than those in model group(P<0.01).The apoptosis rate of hippocampal tissues,expression of Axin protein and GSK-3βlevel in model group were significantly higher than those in sham operation group(P<0.01),while expression ofβ-catenin and Wnt 1 proteins,and activity of PP2A were significantly lower than those in sham operation group(P<0.01).The apoptosis rate of hippocampal tissues,expression of Axin protein and GSK-3βactivity in experimental group were significantly lower than those in model group(P<0.01),while the expressions ofβ-catenin,Wnt 1 proteins and PP2A level were significantly higher than those in model group(P<0.01).Conclusion Quercetin can relieve nerve injury of hippocampal tissues by decreasing the apoptosis rate of hippocampal tissues in AD mice,which may be related to regulating Wnt signaling pathway.
作者
陈方方
白杨
Chen Fangfang;Bai Yang(Department of Neurology,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)
出处
《临床内科杂志》
CAS
2021年第3期195-199,共5页
Journal of Clinical Internal Medicine
基金
新疆维吾尔自治区自然科学基金资助项目(2016DOC233)。
