Relationship between mechanism underlying electroacupuncture-induced reduction of postoperative cognitive dysfunction and microglial NF-κB/NLRP3 signaling pathway in aged mice
10.3760/cma.j.cn131073.20230626.01111
- VernacularTitle:电针减轻老龄小鼠术后认知功能障碍的机制与小胶质细胞NF-κB/NLRP3信号通路的关系
- Author:
Zhibin WEN
1
;
Guangxi LU
;
Luying WANG
;
Da AN
Author Information
1. 哈尔滨医科大学附属第一医院麻醉科，哈尔滨 150000
- Keywords:
Electroacupuncture;
Cognitive dysfunction;
Postoperative complications;
Aged;
NF-kappa B;
NLR family, pyrindomain-containing 3 protein
- From:
Chinese Journal of Anesthesiology
2023;43(11):1335-1340
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the relationship between the mechanism underlying electroacupuncture-induced reduction of postoperative cognitive dysfunction and microglial nuclear factor kappa B (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway in aged mice.Methods:Sixty SPF healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were allocated into 4 groups ( n=15 each) using a random number table method: control group (C group), operation group (O group), operation plus sham electroacupuncture group (O+ SE group) and operation plus electroacupuncture group (O+ Egroup). In O+ E group, the mice received electrical stimulation at the Baihui and Shenting acupoints for a duration of 30 min. The electroacupuncture entailed the utilization of a continuous wave with a frequency of 10 Hz, an intensity of 1 mA, and a daily application for 5 consecutive days. The mice in Y group underwent the same procedure as O+ E group, except that no electrical stimulation was administered. Laparotomy was performed on the mice following a 3% isoflurane anesthesia in O, O+ SE, and O+ E groups. The open field test was conducted in the morning of 6th day after surgery to assess the spontaneous activity and anxiety-like behavior. The novel object recognition test was subsequently performed in the afternoon of 6th day after surgery. The fear conditioning test was performed on 7th day postoperatively. The mice were sacrificed under deep anesthesia at the end of behavioral testing, and the hippocampal tissue was extracted for determination of the expression of phosphorylated NF-κB p65 (p-NF-κB p65), NLRP3, postsynaptic density protein-95 (PSD-95), and synaptic vesicle protein (SYN) (by Western blot) and the co-staining area of NLRP3 and ionized calcium-binding adapter molecule 1 (Iba1, a specific marker for microglia) (by immunofluorescence staining) and for measurement of the dendritic length and dendritic spine density of neurons in the hippocampal CA1 region (using Golgi staining). Results:No statistically significant differences were observed in terms of movement speed, distance traveled, and time of center stay during the open field test among the four groups ( P>0.05). Compared to C group, the percentage of novel object exploration and discrimination index were significantly decreased, the freezing time was prolonged, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was up-regulated, the co-staining area of NLRP3 and Iba1 was increased, the expression of PSD-95 and SYN was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in O, O+ SE and O+ E groups ( P<0.05). Compared to O group, the percentage of novel object exploration and discrimination index were significantly increased, the freezing time was shortened, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was down-regulated, the co-staining area of NLRP3 and Iba1 was decreased, the expression of PSD-95 and SYN was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in O+ E group ( P<0.05), and no significant change was found in each parameter in O+ SE group ( P>0.05). Compared to O+ SE group, the percentage of novel object exploration and discrimination index were significantly increased, the freezing time was shortened, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was down-regulated, the co-staining area of NLRP3 and Iba1 was decreased, the expression of PSD-95 and SYN was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in O+ E group ( P<0.05). Conclusions:The mechanism by which electroacupuncture attenuates postoperative cognitive dysfunction is associated with inhibition of activation of NF-κB/NLRP3 signaling pathway in microglial cells and improvement in synaptic plasticity in aged mice.
