Huangjing Jiannao Granules Improve Learning and Memory Abilities and Cerebral Blood Flow in Rat Model of Vascular Cognitive Impairment via PI3K/Akt Signaling Pathway
10.13422/j.cnki.syfjx.20240836
- VernacularTitle:基于PI3K/Akt信号通路探讨黄精健脑颗粒对血管性认知障碍大鼠学习记忆能力和脑血流量的影响及作用机制
- Author:
Rui YANG
1
;
Yumu TIAN
1
;
Yujing JIN
1
;
Jianwen ZHAIWU
1
;
Tong ZHANG
1
;
Zehua ZHAO
1
;
Shijing HUANG
1
;
Juhua PAN
1
Author Information
1. Guang'anmen Hospital，China Academy of Chinese Medical Sciences， Beijing 100053， China
- Publication Type:Journal Article
- Keywords:
Huangjing Jiannao granules;
vascular cognitive impairment;
cerebral blood flow;
phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway;
neuroinflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(22):52-60
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment （VCI） and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI. MethodSeventy-two SPF-grade male SD rats were randomly selected， with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation （2-VO） for the modeling of VCI. According to the randomized block design， the successfully modeled rats were grouped as follows： model， donepezil hydrochloride （0.50 mg·kg-1）， and low-， medium-， and high-dose （2.36， 4.72， 9.44 g·kg-1， respectively） Huangjing Jiannao granules. After 6 weeks of treatment， Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks， the cerebral blood flow was recorded by a laser microcirculation blood flow imager， and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen （NeuN） in the hippocampus was detected by immunohistochemistry （IHC）. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated protein kinase B （p-Akt）， nuclear factor-κB p65 （NF-κB p65）， and nuclear factor-κB inhibitor α （IκBα） in the hippocampus were determined by Western blot. ResultCompared with the sham operation group， the model group showed weakened learning and memory abilities （P<0.01）， reduced blood flow in the whole brain， forebrain， and hindbrain （P<0.01）， damaged neurons and reduced survived neurons in the hippocampal CA1 region （P<0.01）， down-regulated expression of NeuN （P<0.01）， elevated levels of IL-1β and TNF-α in the serum （P<0.01）， up-regulated protein levels of PI3K， p-Akt， and NF-κB p65 in the hippocampal tissue， and down-regulated protein level of IκBα （P<0.01）. Compared with the model group， medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities （P<0.05，P<0.01）. High-dose Huangjing Jiannao granules increased the blood flow in the whole brain， forebrain， and hindbrain （P<0.05，P<0.01）， and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain （P<0.05）. All the doses of Huangjing Jiannao granules increased the number of survived neurons （P<0.05，P<0.01） and up-regulated the protein level of NeuN （P<0.05，P<0.01）. Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α （P<0.05，P<0.01）， down-regulated the protein levels of PI3K， p-Akt， and NF-κB p65 （P<0.05，P<0.01）， and up-regulated the protein level of IκBα （P<0.01）. ConclusionHuangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway， inhibiting inflammation， and reducing hippocampal neuron injury.
