Huanglian Jiedutang Regulates HIF-1α/VEGF Signaling Pathway to Improve Learning and Memory Abilities of APP/PS1 Transgenic Mice
10.13422/j.cnki.syfjx.20240204
- VernacularTitle:黄连解毒汤调节HIF-1α/VEGF信号通路改善APP/PS1双转基因小鼠学习记忆能力的作用机制
- Author:
Yinghua ZHANG
1
;
Hanlin LYU
2
;
Jianwen ZHOU
3
;
Li FAN
3
;
Yang LI
3
Author Information
1. College of Mental Health，Qiqihar Medical University，Qiqihar 161006，China
2. The First Affiliated Hospital of Qiqihar Medical University，Qiqihar 161041，China
3. Institute of Medical Sciences，Qiqihar Medical University，Qiqihar 161006，China
- Publication Type:Journal Article
- Keywords:
Huanglian Jiedutang （HLJDT）;
β-amyloid precursor protein （APP）/presenilin 1（PS1） transgenic mice;
hypoxia-inducible factor 1α （HIF-1α）;
vascular endothelial growth factor （VEGF）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(7):59-65
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg-1·d-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg-1·d-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.
