Gastrodin improves microglia-mediated inflammatory response after hypoxic-ischemic brain damage in neonatal rats via PI3K/AKT pathway
10.12122/j.issn.1673-4254.2024.09.11
- VernacularTitle:天麻素经PI3K/AKT通路改善新生大鼠缺氧缺血性脑损伤后小胶质细胞介导的炎症反应
- Author:
Hanjun ZUO
1
;
Zhaoda DUAN
;
Zhao WANG
;
Tao GUO
;
Jinsha SHI
;
Haolong SHI
;
Juanjuan LI
Author Information
1. 昆明医科大学基础医学院人体解剖与组织胚胎学系,云南 昆明 650500
- Keywords:
hypoxic-ischemic brain damage;
gastrodin;
inflammatory response;
oxygen and sugar deprivation;
microglia;
PI3K/AKT
- From:
Journal of Southern Medical University
2024;44(9):1712-1719
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.
