Role of NF-κB/NLRP3 signaling pathway in hippocampal microglia in dexmedetomidine-induced improvement in long-term cognitive function after multiple sevoflurane anesthesia in newborn mice
10.3760/cma.j.cn131073.20240312.00608
- VernacularTitle:海马小胶质细胞NF-κB/NLRP3信号通路在右美托咪定改善新生小鼠多次七氟烷麻醉后远期认知功能中的作用
- Author:
Chunhua ZHU
1
;
Zhiqiang NIU
;
Benqing WANG
;
Jian YU
Author Information
1. 沧州市中心医院麻醉科，沧州 061001
- Keywords:
Anesthetics, inhalation;
Infant, newborn;
NF-kappa B;
NLR family, pyrindomain-containing 3 protein;
Cognition disorders
- From:
Chinese Journal of Anesthesiology
2024;44(6):688-693
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of nuclear factor kappa B (NF-κB)/NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) signaling pathway in hippocampal microglia in dexmedetomidine-induced improvement in long-term cognitive function after multiple sevoflurane anesthesia in newborn mice.Methods:One hundred SPF healthy male C57BL/6 mice, aged 6 days, weighing 3-5 g, were divided into 5 groups ( n=20 each) by a random number table method: control group (group C), multiple sevoflurane anesthesia group (group S), multiple sevoflurane anesthesia+ NF-κB inhibitor pyrrolidine dithiocarboxylate group (group SP), multiple sevoflurane anesthesia + dexmedetomidine group (group SD), and multiple sevoflurane anesthesia + NF-κB agonist phorbol 12-myristate 13-acetate (PMA) + dexmedetomidine group (group SPD). Anesthesia was induced by inhalation of 3% sevoflurane and maintained by inhalation of 60% oxygen and 3% sevoflurane for 2 h for 3 consecutive days in S, SP, SD and SPD groups. At 30 min before each sevoflurane inhalation, pyrrolidine dithiocarbamate 100 mg/kg was intraperitoneally injected in group SP, and dexmedetomidine 20 μg/kg was intraperitoneally injected in group SD. NF-κB agonist PMA 15 μg/kg was intraperitoneally injected at 1 h before each sevoflurane inhalation, and 30 min later dexmedetomidine 20 μg/kg was intraperitoneally injected in group SPD. The mice were sacrificed at the age of 11 days, and the hippocampal tissues were isolated for determination of the expression of phosphorylated NF-κB p65 (p-NF-κB p65) and NLRP3 (by Western blot). The co-staining area of NLRP3 and microglia-specific ionized calcium binding adaptor molecule 1 (Iba-1) double positive cells (NLRP3 + -Iba-1 + cells) was calculated by immunofluorescence. The open field test and novel object recognition test were performed at 29 days of age, and the Morris water maze test was performed at 30-34 days of age. Results:There were no significant differences in each parameter of the open field test among the five groups ( P>0.05). Compared with group C, the expression of p-NF-κB p65 and NLRP3 in hippocampal tissues was significantly up-regulated, the co-staining area of NLRP3 + -Iba-1 + cells was increased, the percentage of novel object exploration and discrimination index were decreased, the escape latency was prolonged, and the frequency of crossing the original platform was reduced in group S ( P<0.05). Compared with group S, the expression of p-NF-κB p65 and NLRP3 in hippocampal tissues was significantly down-regulated, the co-staining area of NLRP3 + -Iba-1 + cells was reduced, the percentage of novel object exploration and discrimination index were increased, the escape latency was shortened, and the frequency of crossing the original platform was increased in SP, SD and SPD groups ( P<0.05). Compared with SD group, the expression of p-NF-κB p65 and NLRP3 was significantly up-regulated, the co-staining area of NLRP3 + -Iba-1 + cells was increased, the percentage of novel object exploration and discrimination index were decreased, the escape latency was prolonged, and the number of crossing the original platform location was decreased in SPD group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine improves long-term cognitive function after multiple sevoflurane anesthesia may be related to inhibiting the activation of NF-κB/NLRP3 signaling pathway in the hippocampal microglia of newborn mice.
