Effect of midazolam on neuronal damage in ischemic stroke rats by regulating the PINK1/PARKIN signaling pathway
10.12206/j.issn.2097-2024.202405024
- VernacularTitle:咪达唑仑调节PINK1/PARKIN信号通路对缺血性脑卒中大鼠神经元损伤的影响
- Author:
Junli ZHANG
1
;
Yuanyuan LI
1
;
Jing YIN
1
;
Hongyuan YANG
1
;
Yaowu BAI
1
Author Information
1. Department of Anesthesiology, Tangshan Maternal and Child Health Care Hospital, Tangshan 063000, China.
- Publication Type:Originalarticles
- Keywords:
midazolam;
PINK1/PARKIN signaling pathway;
ischemic stroke;
neuron;
autophagy;
apoptosis
- From:
Journal of Pharmaceutical Practice and Service
2025;43(6):288-292
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.
