瑞马唑仑通过抑制AKT1/GSK-3β信号通路减轻切口痛模型大鼠的术后痛觉过敏

马家慧; 韦凯斌; 张振; 李越; 吴立新

瑞马唑仑通过抑制AKT1/GSK-3β信号通路减轻切口痛模型大鼠的术后痛觉过敏

Study on the remimazolam alleviating the postoperative hyperalgesia in incision pain model rats by inhibiting the AKT1/GSK-3β signaling pathway

摘要

摘要:
目的： 分析瑞马唑仑通过抑制丝氨酸苏氨酸蛋白激酶（AKT1）/糖原合成酶激酶-3β（GSK-3β）信号通路对切口痛模型大鼠的术后痛觉过敏的影响。
方法： 30只建模大鼠，最终建模成功模型组（n = 9）给予0.9%氯化钠溶液、瑞马唑仑组（n = 10）给予瑞马唑仑、瑞马唑仑 + 激动剂组（n = 9）给予瑞马唑仑 + AKT1激动剂，空白组（n = 10）给予0.9%氯化钠溶液。检测对比各组足反射阈值（MWT）、致痛物质、炎性因子水平、AKT1、GSK-3β mRNA表达量及相对表达量。
结果： 各组造模前MWT水平对比（P ＞ 0.05）；造模后6 h、12 h、24 h，与空白组相比，各组MWT水平降低（P ＜ 0.05）；与模型组相比，瑞马唑仑组、瑞马唑仑 + 激动剂组MWT水平升高（P ＜ 0.05）；与瑞马唑仑组相比，瑞马唑仑 + 激动剂组MWT水平降低（P ＜ 0.05）。与空白组相比，各组神经激肽-1受体（NK-1R）、P物质（SP）、白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）、IL-1β水平、AKT1、GSK-3β mRNA表达量及相对表达量升高（P ＜ 0.05）；与模型组相比，瑞马唑仑组、瑞马唑仑 + 激动剂组NK-1R、SP、IL-6、TNF-α、IL-1β水平、AKT1、GSK-3β mRNA表达量及相对表达量降低（P ＜ 0.05）；与瑞马唑仑组相比，瑞马唑仑 + 激动剂组NK-1R、SP、IL-6、TNF-α、IL-1β水平、AKT1、GSK-3β mRNA表达量及相对表达量升高（P ＜ 0.05）。
结论： 切口痛模型大鼠采用瑞马唑仑干预后疼痛阈值提升，痛觉过敏缓解，炎性反应减轻，其机制可能与AKT1/GSK-3β信号通路受抑有关。

Abstract:
Objective To analyze the effects of remimazolam on postoperative hyperalgesia in incision pain model rats by inhibiting the serine threonine protein kinase (AKT1)/glycogen synthase kinase-3β(GSK-3β) signaling pathway.
Methods Thirty modeling rats were used, the model group (n = 9) were given 0.9% sodium chloride solution, the remimazolam group (n = 10) were given remimazolam, the remimazolam + agonist group (n = 9) were given remimazolam + AKT1 agonist, and the blank group (n = 10) were given 0.9% sodium chloride solution. The foot reflex threshold (MWT), pain-causing substances, levels of inflammatory factors, expression levels and relative expression levels of AKT1 and GSK-3β mRNA in four groups were detected and compared.
Results There was no statistical significance in the MWT levels among four groups before modeling (P ＞ 0.05). After 6 hours, 12 hours and 24 hours of modeling, compared with the blank group, the MWT levels in other three groups decreased (P ＜ 0.05); compared with the model group, the MWT levels in the remimazolam group and remimazolam + agonist group increased (P ＜ 0.05); compared with the remimazolam group, the MWT level in the remimazolam + agonist group decreased (P ＜ 0.05). Compared with the blank group, the levels of neurokinin-1 receptor (NK-1R), substance P(SP), interleukin (IL) -6, tumor necrosis factor -α(TNF-α), IL-1β and mRNA, protein expression levels of AKT1 and GSK-3β in others three group increased (P ＜ 0.05). Compared with the model group, the levels of NK-1R, SP, IL-6, TNF-α and IL-1β and mRNA, protein expression levels of AKT1 and GSK-3β in the remimazolam group and remimazolam + agonist group decreased (P ＜ 0.05). Compared with the remimazolam group, the levels of NK-1R, SP, IL-6, TNF-α, IL-1β and mRNA, protein expression levels of AKT1 and GSK-3β in the remimazolam + agonist group increased (P ＜ 0.05).
Conclusions After intervention with remimazolam in the incision pain model rats, the pain threshold increases, the hyperalgesia relieves, and the inflammatory reactions reduce. The mechanism may be related to the inhibition of the AKT1/GSK-3β signaling pathway.

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