目的 探讨羟考酮是否通过影响AMPK/SIRT1信号通路改善老年骨折模型术后认知功能下降。方法 将SD大鼠随机分为假手术组、模型组及10、20、30 μg·kg⁻¹·d⁻¹羟考酮剂量组,每组10只。采用开放性胫骨骨折手术构建老年骨折术后认知功能障碍模型。给药2周后,采用Morris水迷宫实验评估认知功能,HE染色和Nissl染色观察海马病理损伤及神经元数量,ELISA检测海马组织中白细胞介素（interleukin,IL）-1β、IL-18、肿瘤坏死因子-α（tumor necrosis factor,TNF-α）水平,Western blot检测海马组织中p-AMPK/AMPK、SIRT1、p-NF-κB/NF-κB蛋白表达水平。结果 相对于假手术组,模型组大鼠认知功能显著下降,海马组织呈现病理性损伤及神经元数量减少,海马组织中IL-1β、IL-18、TNF-α等促炎因子的表达显著上调,海马组织中p-AMPK/AMPK、SIRT1蛋白表达下调而p-NF-κB/NF-κB蛋白表达显著上调。经20、30 μg·kg⁻¹·d⁻¹羟考酮处理后,模型大鼠上述现象均得到明显改善,其中高剂量效果更佳。结论 羟考酮可能通过激活AMPK/SIRT1信号通路,抑制海马促炎因子表达,进而改善老年骨折模型术后认知功能下降。
Abstract
Objective To explore whether oxycodone improves postoperative cognitive decline in elderly fracture models by affecting the AMPK/SIRT1 signaling pathway. Methods SD rats were randomly divided into sham operation group, model group, and 10, 20, and 30 μg·kg-¹·d-¹ oxycodone dose groups, with 10 rats in each group Open tibial fracture surgery was used to construct a model of cognitive dysfunction after fracture surgery in the elderly After 2 weeks of dosing, cognitive function was assessed using the Morris water maze test. The pathological injury of hippocampus and the number of neurons in hippocampus were observed by HE staining and Nissl staining, and the level of interleukin (IL) -1β, IL-18, tumor necrosis factor-α (TNF-α) in hippocampus was detected by ELISA. The level of p-AMPK/AMPK, SIRT1, p-NF-κB/NF-κB protein in hippocampus was detected by Western blot. Results Compared with the sham operation group, the model group showed a notable decrease in cognitive function (P<0.05), and the hippocampal tissue presented pathological damage, and the number of neurons in hippocampus decreased, and the IL-1β, IL-18 and TNF-α in hippocampus up-regulated whereas the p-AMPK/AMPK and SIRT1 down-regulated (P<0.05). After the treatment of 20, 30 μg·kg-¹·d-¹ oxycodone, the above phenomena were significantly improved, and the high dose was better. Conclusion Oxycodone may inhibit the expression of hippocampal pro-inflammatory factors by activating the AMPK/SIRT1 signaling pathway, thereby improving the postoperative cognitive decline in elderly fracture models
关键词
羟考酮 /
AMPK/SIRT1信号通路 /
老年骨折 /
术后认知功能下降
Key words
oxycodone /
AMPK/SIRT1 signaling pathway /
senile fracture /
postoperative cognitive decline
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基金
无锡市卫生健康委科研项目 “基于脑-肠轴理论探究电针疗法对老年患者围术期神经认知障碍的临床疗效及作用机制”（Q202260）
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