Effects of Ditan Yizhi Decoction on Mitochondrial Autophagy in Rats with Vascular Dementia Based on Wnt/β-catenin Signaling Pathway
10.19879/j.cnki.1005-5304.202410470
- VernacularTitle:基于Wnt/β-catenin信号通路探讨涤痰益智汤对血管性痴呆大鼠线粒体自噬的影响
- Author:
Mengyu GU
1
;
Lieqian SUN
;
Jie YANG
;
Kaiyi WANG
;
Fan WU
;
Chao YANG
;
Li ZHENG
;
Xiangzhong SHEN
Author Information
1. 湖北中医药大学,湖北 武汉 430061;湖北省中西医结合医院,湖北 武汉 430015
- Publication Type:Journal Article
- Keywords:
vascular dementia;
Ditan Yizhi Decoction;
Wnt/β-catenin signaling pathway;
mitophagy;
rats
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(5):127-133
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effects of Ditan Yizhi Decoction on Wnt/β-catenin signaling pathway and mitochondrial autophagy in vascular dementia(VD)rats.Methods Totally 70 male SD rats were randomly selected as the sham-operation group,with only the common carotid artery isolated and not ligated,and the rest of the rats were used to prepare a rat model of VD by the modified bilateral common carotid artery permanent ligature method.The successfully modeled rats were randomly divided into model group,donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups and were given corresponding interventions for 4 weeks.Morris water maze experiment was used to assess the learning and memory ability of rats,HE staining and Nissl staining were used to observe the morphology of hippocampal tissue,transmission electron microscopy was used to observe the ultrastructure of hippocampal neuron,Western blot was used to detect the expressions of PINK1,Parkin,p62,Beclin-1,LC3BⅡ/Ⅰ,β-catenin,GSK-3β,p-GSK-3β protein.Results Compared with the sham-operation group,rats in the model group had a prolonged escape latency(P<0.01),a reduced number of crossing platforms(P<0.01);neuronal gaps in the CA1 area of the hippocampus were enlarged,with irregular cell morphology and blurred borders,neuronal solidification,Nissl bodies dissolution and fragmentation,reduced quantity,mitochondrial cristae disorder,and disruption of the structure of the bilayer membrane,with a greater number of autophagosomes in the surroundings;the expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/I,β-catenin,p-GSK-3β/GSK-3β protein were significantly increased(P<0.01),and p62 protein expression was significantly decreased(P<0.01).Compared with the model group,the escape latency of rats in donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups were significantly shortened(P<0.01),and the number of crossing platforms significantly increased(P<0.05,P<0.01);the number of neurons in the hippocampal CA1 region increased,with normal morphology and orderly arrangement,Nissl bodies were abundant,and transmission electron microscopy showed that mitochondrial morphology recovered,rupture decreased,and autophagosomes around mitochondria decreased,the protein expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/Ⅰ,β-catenin and p-GSK-3β/GSK-3β in hippocampal tissue were significantly decreased(P<0.01),the protein expression of p62 significantly increased(P<0.05,P<0.01).Conclusion Ditan Yizhi Decoction can improve learning memory ability and neuronal morphology in VD rats,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway to inhibit mitophagy.
