浙江中医药大学学报2025，Vol.49Issue(10)：1233-1241,9.DOI:10.16466/j.issn1005-5509.2025.10.003
地黄饮子通过维生素D轴介导Ca2+-Calpain-CDK5信号通路治疗AD肾虚精亏证
Dihuang Yinzi Decoction Treats Kidney Essence Deficiency Syndrome of AD through Ca2+-Calpain-CDK5 Signaling Pathway Mediated by Vitamin D Axis
摘要
Abstract
[Objective]To explore the mechanism of Dihuang Yinzi Decoction on kidney essence deficiency syndrome of Alzheimer's disease(AD)based on vitamin D axis(VD axis)-Ca2+-Calpain-cyclin-dependent kinase 5(CDK5)signaling pathway.[Methods]Thirty-six SD rats were randomly divided into control group,model group,Dihuang Yinzi Decoction low-dose group(5.36 g/kg),medium-dose group(10.72 g/kg),high-dose group(21.45 g/kg)and donepezil group(0.25 mg/kg).First,model of kidney essence deficiency syndrome was established in rats through intraperitoneal injection of D-galactose.Subsequently,an AD model with kidney essence deficiency syndrome was developed by injecting Aβ25-35 bilaterally into the CA1 region of the hippocampus.Morris water maze experiment was used to observe the behavioral changes of each group of mice.The concentrations of 25-hydroxyvitamin D3[25(OH)D3],1,25-dihydroxyvitamin D3[1,25-(OH)2D3]and Ca2+in serum were detected by enzyme-linked immunosorbent assay(ELISA).The ultrastructure of neurons in hippocampus was observed by transmission electron microscope.The expression levels of Calpain 1,CDK5,p35,p25,tau,phospho-tau Thr205(pT205)and phospho-tau Ser396(pS396)in hippocampus were detected by Western blot.[Results]Compared with model group,behavioral experiment showed Dihuang Yinzi Decoction can relieve the cognitive impairment and anxiety-like behaviors of AD kidney essence deficiency syndrome model rats(P<0.01).ELISA results showed that after Dihuangyinzi Decoction treatment,the concentrations of 25(OH)D3 and 1,25-(OH)2D3 in the rat serum increased(P<0.05,P<0.01),while the Ca2+concentration decreased(P<0.05,P<0.01).Transmission electron microscopy showed that Dihuang Yinzi Decoction improved the structural morphology of hippocampal neurons and alleviated mitochondrial swelling.Western blot showed that Dihuang Yinzi Decoction decreased the protein expressions of Calpain 1,CDK5,p25,tau,pT205 and pS396(P<0.01,P<0.05),and increased the protein expression of p35(P<0.05).[Conclusion]Dihuang Yinzi Decoction can regulate the cognitive ability of rats with AD kidney essence deficiency syndrome by regulating the VD axis-Ca2+-Calpain-CDK5 signaling pathway,and protect hippocampal nerve cells.关键词
肾虚精亏证/阿尔茨海默病/地黄饮子/海马神经元/维生素D轴/Ca2+/Calpain/CDK5Key words
kidney essence deficiency syndrome/Aizheimer's disease/Dihuang Yinzi Decoction/hippocampal neurons/vitamin D axis/calcium ion/Calpain/CDK5分类
医药卫生引用本文复制引用
成金枝,高永强,田永仪,贺文彬,闫金宙,陈伊旻,郭紫娟..地黄饮子通过维生素D轴介导Ca2+-Calpain-CDK5信号通路治疗AD肾虚精亏证[J].浙江中医药大学学报,2025,49(10):1233-1241,9.基金项目
山西省基础研究计划自由探索类自然科学研究面上项目(202203021221286) Natural Science Research Program of Free Exploration of Shanxi Basic Research Project(202203021221286) （202203021221286）
