Midazolam alleviates neuronal damage induced by oxygen glucose deprivation/restoration in mice
10.16352/j.issn.1001-6325.2024.04.0459
- VernacularTitle:咪达唑仑减轻氧糖剥夺/复糖复氧诱导的小鼠神经元损伤
- Author:
Tao CHEN
1
;
Lingjun CHEN
;
Yuan LI
Author Information
1. 永州市中心医院冷水滩院区 麻醉科,湖南 永州 425000
- Keywords:
midazolam;
oxygen glucose deprivation/restoration;
neuron
- From:
Basic & Clinical Medicine
2024;44(4):459-466
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of midazolam on neuronal injury induced by oxygen glucose depri-vation/reoxygenation(OGD/R)in mice.Methods An injury model of neuronal cell line HT22 was established by OGD/R induction.HT22 cells were divided into OGD/R group,low-dose group,medium-dose group and high-dose group,midazolam+KG-501(CREB inhibitor)group and control group.ELISA was applied to detect TNF-α and IL-6 levels;Commercialy available reagent kits were applied to detect superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels;MTT and Edu experiments were applied to detect cell prolifera-tion;flow cytometry was applied to detect cell apoptosis rate;RT-qPCR method was applied to detect the ex-pression levels of CREB mRNA and PGC-1α mRNA;Western blot was applied to detect the expression levels of Ki-67,Bcl-2,Bax,CREB,and PGC-1α proteins.Results Compared with the control group,the A490 value(24,48 hours),proliferation rate,SOD and CAT activity,CREB mRNA and PGC-1α mRNA expres-sion,Ki-67,Bcl-2,CREB,and PGC-1α protein level in the OGD/R group were all significantly reduced(P<0.05);The apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were significanty increased(P<0.05).Compared with the OGD/R group,the A490 values(24,48 hours),proliferation rate,SOD,CAT activity,CREB mRNA and PGC-1α mRNA expression,and Ki-67,Bcl-2,CREB,and PGC-1α protein expression were significantly increased in low,medium,and high dose midazolam groups;The apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were obviously reduced(P<0.05).Compared with the high-dose midazolam group,A490 value(24,48 hours),proliferation rate,activity of SOD and CAT,CREB mRNA and PGC-1α mRNA expression as well as Ki-67,Bcl-2,CREB,and PGC-1α protein expression were all sig-nificantlu reduced in the high-dose midazolam+KG-501 group while the apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were obviously increased(P<0.05).Conclusions Midazolam might alleviate nerve cell injury potentially through the mechaninsms of promoting OGD/R-induced proliferation and reducing cell apoptosis in HT22 cells.