Dihuang Yinzi Decoction Treats Kidney Essence Deficiency Syndrome of AD through Ca2+-Calpain-CDK5 Signaling Pathway Mediated by Vitamin D Axis
10.16466/j.issn1005-5509.2025.10.003
- VernacularTitle: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
- Author:
Jinzhi CHENG
1
;
Yongqiang GAO
;
Yongyi TIAN
Author Information
1. 山西中医药大学附属医院 太原 030024;山西中医药大学分子中医药学国家国际联合研究中心 中医脑病学山西省重点实验室
- Publication Type:Journal Article
- Keywords:
kidney essence deficiency syndrome;
Aizheimer's disease;
Dihuang Yinzi Decoction;
hippocampal neurons;
vitamin D axis;
calcium ion;
Calpain;
CDK5
- From:
Journal of Zhejiang Chinese Medical University
2025;49(10):1233-1241
- CountryChina
- Language:Chinese
-
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.
