Role of Nrf2/NLRP3 signaling pathway in propofol postconditioning-induced reduction of hippocampal neuron injury in a rat model of oxygen-glucose deprivation and restoration
10.3760/cma.j.cn131073.20230321.00816
- VernacularTitle:Nrf2/NLRP3信号通路在丙泊酚后处理减轻氧糖剥夺-复糖复氧大鼠海马神经元损伤中的作用
- Author:
Min ZHU
1
;
Hongli YU
;
Ying SUN
;
Hongxia LI
;
Hengchang REN
;
Wenli YU
Author Information
1. 天津医科大学一中心临床学院，天津 300192
- Keywords:
NF-E2-Related Factor 2;
NLR family, pyrin domain-containing 3 protein;
Propofol;
Ischemic postconditioning;
Hippocampus;
Neurons;
Hypoxia
- From:
Chinese Journal of Anesthesiology
2023;43(8):977-980
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway in propofol postconditioning-induced reduction of hippocampal neuron injury in a rat model of oxygen-glucose deprivation and restoration (OGD/R).Methods:The hippocampal neurons were isolated from fetal rats of Wistar rats at 16-18 days of gestation and primarily cultured for 7 days and then divided into 4 groups ( n=42 each) using a random number table method: control group (group C), OGD/R group (group O), propofol post-conditioning group (group P) and Nrf2 siRNA(-) transfection group (group N). The cells were routinely cultured in group C. The cells were subjected to oxygen-glucose deprivation for 1 h followed by oxygen and glucose supply in group O. Propofol (final concentration 1.2 μg/ml) was added immediately after oxygen and glucose supply, the cells were then cultured for 2 h, and the culture medium was replaced with the normal culture medium in group P. The primarily cultured neurons were transfected with Nrf2 gene knockout lentivirus on 3rd day of culture, 24 h later the cells were then routinely cultured, and the model was prepared and propofol conditioning was performed on 7th day. Cells were collected at 24 h of incubation for determination of the cell apoptosis (by flow cytometry), expression of Nrf2 and NLRP3 mRNA and protein (using quantitative real-time polymerase chain reaction or Western blot), concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β, and activities of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (kit method). Results:Compared with group C, the apoptosis rate of neurons was significantly increased, concentrations of TNF-α, IL-6 and IL-1β were increased, the levels of GSH, SOD and CAT were decreased, the expression of Nrf2 and NLRP3 protein and mRNA was up-regulated, and the nuclear/plasma ratio of Nrf2 was increased in O and P groups ( P<0.05). Compared with group O, the apoptosis rate of neurons was significantly decreased, the concentrations of TNF-α, IL-6 and IL-1 β were decreased, the levels of GSH, SOD and CAT were increased, the expression of Nrf2 protein and mRNA was up-regulated, the nuclear/plasma ratio of Nrf2 was increased, and the expression of NLRP3 protein and mRNA was down-regulated in group P ( P<0.05). Compared with group P, the apoptosis rate of neurons was significantly increased, concentrations of TNF-α, IL-6 and IL-1β were increased, the levels of GSH, SOD and CAT were decreased, the expression of Nrf2 protein and mRNA was down-regulated, the nuclear/plasma ratio of Nrf2 was decreased, and the expression of NLRP3 protein and mRNA was up-regulated in group N ( P<0.05). Conclusions:Nrf2/NLRP3 signaling pathway is involved in propofol postconditioning-induced reduction of hippocampal neuron injury in a rat model of OGD/R.
