核因子-κB/P65信号通路：七氟醚麻醉后术后认知功能障碍的潜在治疗靶点
NF-κB/P65 signaling pathway: a potential therapeutic target in postoperative cognitive dysfunction after sevoflurane anesthesia.
作者信息
Zheng J-W, Meng B, Li X-Y, Lu B, Wu G-R, Chen J-P
机构信息
Department of Anesthesiology, Ningbo No. 2 Hospital, Ningbo, China.
出版信息
Eur Rev Med Pharmacol Sci. 2017 Jan;21(2):394-407.
OBJECTIVE
This study aimed to explore the role of NF-κB/P65 signaling pathway in postoperative cognitive dysfunction (POCD) after sevoflurane anesthesia.
MATERIALS AND METHODS
A total of 120 male Sprague-Dawley (SD) rats were selected and assigned into five groups (24 rats in each group): the control, sevoflurane, sevoflurane + splenectomy, pyrrolidine dithiocarbamate (PDTC, a specific inhibitor of NF-κB), and sevoflurane + splenectomy + PDTC groups. Electrocardiogram (ECoG) and behavior changes of rats were monitored before and after anesthesia/operation. Ionized calcium-binding adapter molecules 1 (Iba-1) in the hippocampal zones were observed by immunofluorescence staining. Blood-brain barrier (BBB) permeability was determined by immunohistochemistry. The mRNA and protein expressions of NF-κB/P65 signaling pathway-related proteins and inflammatory cytokines were detected by qRT-PCR assay and Western blotting.
RESULTS
During the anesthesia/operation, the vital signs of rats were stable, but the ECoG in the sevoflurane and sevoflurane + splenectomy groups mainly presented slow waves. The ECoG arousal response in the sevoflurane + splenectomy + PDTC group was observed. At 24 h after the anesthesia/operation, the expressions of NF-κB and P65 in the hippocampal zone, the expressions of IκBα and inflammatory cytokines (IL-1β, IL-6 and TNF-α), the expression of Iba-1 in rat hippocampal dentate gyrus (DG) zone and CA3 zone, and the permeability of BBB were significantly increased and the behavior of rats changed dramatically (all p < 0.05), while PDTC treatments could eliminate these changes induced by the anesthesia/operation (all p < 0.05). No changes were observed in the expressions of NF-κB, P65, IκBα, Iba-1 and inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the permeability of BBB and the behavior of rats in the sevoflurane and the PDTC groups (all p > 0.05).
CONCLUSIONS
These results suggest that the inhibition of NF-κB/P65 signaling pathway may relieve POCD after sevoflurane anesthesia.
目的
本研究旨在探讨核因子κB（NF-κB）/P65信号通路在七氟醚麻醉后术后认知功能障碍（POCD）中的作用。
材料与方法
选取120只雄性Sprague-Dawley（SD）大鼠，分为五组（每组24只）：对照组、七氟醚组、七氟醚+脾切除组、吡咯烷二硫代氨基甲酸盐（PDTC，NF-κB的特异性抑制剂）组以及七氟醚+脾切除+PDTC组。监测大鼠麻醉/手术前后的心电图（ECoG）和行为变化。通过免疫荧光染色观察海马区离子钙结合衔接分子1（Iba-1）。采用免疫组织化学法测定血脑屏障（BBB）通透性。通过qRT-PCR检测和蛋白质印迹法检测NF-κB/P65信号通路相关蛋白及炎性细胞因子的mRNA和蛋白表达。
结果
麻醉/手术期间，大鼠生命体征平稳，但七氟醚组和七氟醚+脾切除组的ECoG主要表现为慢波。观察到七氟醚+脾切除+PDTC组的ECoG觉醒反应。麻醉/手术24小时后，海马区NF-κB和P65的表达、IκBα及炎性细胞因子（IL-1β、IL-6和TNF-α）的表达、大鼠海马齿状回（DG）区和CA3区Iba-1的表达以及BBB通透性均显著增加，大鼠行为变化显著（均p<0.05），而PDTC处理可消除麻醉/手术诱导的这些变化（均p<0.05）。七氟醚组和PDTC组大鼠的NF-κB、P65、IκBα、Iba-1及炎性细胞因子（IL-1β、IL-6和TNF-α）的表达、BBB通透性及行为均未观察到变化（均p>0.05）。
结论
这些结果表明，抑制NF-κB/P65信号通路可能减轻七氟醚麻醉后的POCD。
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