Midazolam alleviates neuronal damage induced by oxygen glucose deprivation/restoration in mice
CHEN Tao, CHEN Lingjun, LI Yuan
2024, 44(4):
459-466.
doi:10.16352/j.issn.1001-6325.2024.04.0459
Asbtract
(
78 )
PDF (5488KB)
(
79
)
References |
Related Articles |
Metrics
Objective To investigate the impact of midazolam on neuronal injury induced by oxygen glucose deprivation/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 proliferation; flow cytometry was applied to detect cell apoptosis rate; RT-qPCR method was applied to detect the expression 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 expression, 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 significantlu 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.