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 protein β-secretory enzyme,BACE1)、过度磷酸化tau蛋白(over-phosphorylated tau protein,P-Tau396)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-Tau396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-Tau396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 protein β-secretase (BACE1), over-phosphorylated tau protein (P-Tau396), cyclin-dependent protein kinase 5(CDK5), estrogen receptor β(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-Tau396, CDK5 and P-P38/P38 in hippocampus increased significantly (P<0.01), while the expression level of ERβ decreased significantly (P<0.01). TFRD could improve the behavioral performance of mice in different models, decrease the expression levels of APP、BACE1、P-Tau396、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.
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