Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis
10.13422/j.cnki.syfjx.20231817
- VernacularTitle:基于微生物-脑-肠轴探讨益气解毒方抗缺血性脑卒中作用机制
- Author:
Jialin YANG
1
;
Bingjie CAI
2
;
Yuhao DAI
1
;
Shuting LI
1
;
Keke ZHANG
3
;
Yanhua GAO
1
;
Qiman ZHANG
1
;
Ying ZHANG
4
;
Jianying SHEN
1
;
Shaojing LI
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China
2. Anhui University of Chinese Medicine， Hefei 230000， China
3. Changsha College of Health Professions， Changsha 410100， China
4. Beijing City University， Beijing 100083， China
- Publication Type:Journal Article
- Keywords:
Yiqi Jiedu formula;
intestinal microbiota;
microbiota-gut-brain axis;
ischemic stroke;
16S rDNA
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(6):91-100
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.
