骨碎补总黄酮对亚硝酸钠模型小鼠学习记忆能力的改善作用

Improvement effects of total flavonoids of Rhizoma Drynariae on learning and memory in sodium nitrite model mice

目的:研究骨碎补总黄酮对亚硝酸钠模型小鼠学习记忆障碍的改善作用。方法:昆明雄性小鼠随机分为空白组、亚硝酸钠模型组100 mg/(kg·d)、抗脑衰胶囊组585 mg/(kg·d)、骨碎补总黄酮97.5 mg/(kg·d)、骨碎补总黄酮组+ER阻断剂组97.5 mg/(kg·d)+0.072 mg/(kg·d)。观察小鼠的学习记忆能力,HE染色观察海马病理形态;Western blot法观察海马区淀粉样蛋白前体蛋白(amyloid precursor protein,APP)、淀粉样前体蛋白β-分泌酶(amyloid precursor proteinβ-secretory enzyme,BACE1)、过度磷酸化tau蛋白(over-phosphorylated tau protein,P-Tau^(396))和细胞周期素依赖蛋白激酶5(cyclin-dependent protein kinase 5,CDK5)蛋白含量。结果:模型组学习行为能力降低,海马区颗粒细胞明显坏死,海马区APP、BACE1、P-Tau^(396)和CDK5表达水平升高(P<0.01)。骨碎补总黄酮能够改善模型小鼠的行为学表现,降低APP、BACE1、P-Tau^(396)和CDK5的表达(P<0.01)。ER阻断剂能够反转骨碎补总黄酮在以上指标蛋白中的作用。结论:骨碎补总黄酮对亚硝酸钠模型小鼠学习记忆能力具有改善作用,此效应与调节APP代谢途径相关蛋白的影响相关。

Objective:To study the effect of total flavonoids of Rhizoma Drynariae(TFRD)on learning and memory impairment of sodium nitrite model mice.Methods:KM mice were randomly divided into the blank group,sodium nitrite model group 100 mg/(kg·d),Kangnaoshuai capsule group 585 mg/(kg·d),TFRD group 97.5 mg/(kg·d),and the TFRD+ER blocker group 97.5 mg/(kg·d)+0.072 mg/(kg·d).The learning and memory ability of mice were observed.Morphology of hippocampus was detected with HE staining.The contents of amyloid precursor protein(APP),amyloid precursor proteinβ-secretase(BACE1),over-phosphorylated tau protein(P-Tau^(396)),cyclin-dependent protein kinase 5(CDK5),estrogen receptorβ(ERβ)and phosphorylated p38(p-p38)in hippocampus were tested with Western blot.Results:The learning ability of mice in the model group decreased significantly.Granular cells in hippocampus were obviously necrotic.The expression levels of APP,BACE1,P-Tau^(396),CDK5 and P-P38/P38 in hippocampus increased significantly(P<0.01),while the expression level of ERβdecreased significantly(P<0.01).TFRD could improve the behavioral performance of mice in different models,decrease the expression levels of APP、BACE1、P-Tau^(396)、CDK5 and P-P38/P38(P<0.01),and increase the expression levels of ERβ.ER blocker could reverse the effect of TRFD on the above proteins.Conclusion:TFRD could improve learning and memory ability of mice in sodium nitrite model,which may due to the effect of TFRD on regulating proteins related to APP metabolic pathway.