Oxycodone Activates AMPK/SIRT1 Signaling Pathway to Alleviate Cognitive Function Decline after Surgery in Elderly Fracture Model of SD Rats

SUN Hai, HUANG Teng, MAO Dongyu, LI Rong hua, REN Xiaoping, ZHU Ping

Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (6) : 134-139.

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (6) : 134-139.
Clinical Medicine

Oxycodone Activates AMPK/SIRT1 Signaling Pathway to Alleviate Cognitive Function Decline after Surgery in Elderly Fracture Model of SD Rats

  • SUN Hai, HUANG Teng, MAO Dongyu, LI Rong hua, REN Xiaoping, ZHU Ping
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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

Key words

oxycodone / AMPK/SIRT1 signaling pathway / senile fracture / postoperative cognitive decline

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SUN Hai, HUANG Teng, MAO Dongyu, LI Rong hua, REN Xiaoping, ZHU Ping. Oxycodone Activates AMPK/SIRT1 Signaling Pathway to Alleviate Cognitive Function Decline after Surgery in Elderly Fracture Model of SD Rats[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(6): 134-139

References

[1] TRAVERS R, GAGLIARDI G, RAMSEYER M.Delirium management in perioperative geriatric services: a narrative review of non-pharmaceutical strategies[J]. Front Psychiatry, 2024, 15: 1394583.
[2] SCHAEFER ST, KOENIGSPERGER S, OLOTU C, et al.Biomarkers and postoperative cognitive function: could it be that easy?[J]Curr Opin Anaesthesiol, 2019, 32(1): 92-100.
[3] SURAARUNSUMRIT P, SRINONPRASERT V, KONGMALAI T, et al. Outcomes associated with postoperative cognitive dysfunction: a systematic review and meta-analysis[J]. Age Ageing, 2024, 53(7): afae160.
[4] LOU L, YU W, CHENG Y, et al.Quercetin can improve anesthesia induced neuroinflammation and cognitive dysfunction by regulating miR-138-5p/ LCN2[J]. BMC Anesthesiol, 2025, 25(1): 21.
[5] 易姝彤. 右美托咪定联合羟考酮超前镇痛对胆囊切除患者术后认知功能障碍的影响[D]. 广州: 广州医科大学, 2023.
[6] XIAO QX, LIU Q, DENG R, et al.Postoperative cognitive dysfunction in elderly patients undergoing hip arthroplasty[J]. Psychogeriatrics, 2020, 20(4): 501-509.
[7] CZYŻ-SZYPENBEJL K, Mędrzycka-Dąbrowska W, Kwiecień-Jaguś K, et al.The Occurrence of Postoperative Cognitive Dysfunction (POCD) - Systematic Review[J]. Psychiatr Pol, 2019, 53(1): 145-160.
[8] XIONG B, YANG C, YANG X, et al.Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1G93A transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1β/NF-κB pathways[J]. CNS Neurosci Ther, 2024, 30(6): e14692.
[9] JIA P, CHE J, ZHANG J, et al.Metformin ameliorates postoperative cognitive dysfunction through regulation of the AMPK/SIRT1 pathway[J]. J Integr Neurosci, 2023, 22(5): 110.
[10] 杨清龄, 赵继波, 袁明霞, 等. 布托啡诺减轻老年大鼠胫骨骨折术后认知功能障碍的作用机制研究[J]. 中国药师, 2021, 24(8): 440-444.
[11] 张璐, 王玉. 羟考酮对神经病理性痛大鼠脊髓背角蛋白表达的影响[J]. 中国临床药理学杂志, 2019, 35(14): 1470-1473.
[12] 方军, 董庆永, 刘志东, 等. 羟考酮通过TLR4/p38MAPK通路抑制小胶质细胞的活化缓解大鼠骨癌痛[J]. 中国免疫学杂志, 2023, 39(11): 2355-2360.
[13] 董晶晶, 温哲, 周南, 等. 右美托咪定改善老年大鼠股骨颈骨折术后认知功能[J]. 解剖科学进展, 2024, 30(03): 233-236, 239.
[14] ZHANGCY, YANG YS, PEI MQ, et al.The association of cerebral oxygen desaturation with postoperative cognitive dysfunction in older patients: a review[J]. Clin Interv Aging, 2024, 19: 1067-1078.
[15] AREFAYNE NR, BERHE YW, VAN ZUNDERTAA.Incidence and factors related to prolonged postoperative cognitive decline (POCD) in elderly patients following surgery and anaesthesia: a systematic review[J]. J Multidiscip Healthc, 2023, 16: 3405-3413.
[16] SHEN J, XU J, WEN Y, et al.Carnosine ameliorates postoperative cognitive dysfunction of aged rats by limiting astrocytes pyroptosis[J]. Neurotherapeutics, 2024, 21(4): e00359.
[17] LIN QC, WANG J, WANG XL, et al.Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice[J]. Biochim Biophys Acta Mol Basis Dis, 2024, 1870(5): 167137.
[18] ZHOU Y, ZHANG Y, WANG H, et al.Microglial pyroptosis in hippocampus mediates sevolfurane-induced cognitive impairment in aged mice via ROS-NLRP3 inflammasome pathway[J]. Int Immunopharmacol, 2023, 116: 109725.
[19] WEN Q, SUN D, YANG L, et al.Impact of butorphanol versus sufentanil on postoperative cognition and inflammation in elderly: a pilot study[J]. Front Aging Neurosci, 2024, 16: 1395725.
[20] 陈喜苹, 黄金珠, 李永格. 盐酸羟考酮对癫痫大鼠炎症和神经元凋亡的影响及机制研究[J]. 中华老年心脑血管病杂志, 2023, 25(10): 1093-1097.
[21] 田园, 杨海昌, 李秀华, 等. 羟考酮预处理对老龄脑缺血再灌注损伤大鼠的脑保护的作用[J]. 中国临床药理学杂志, 2023, 39(17): 2517-2521.
[22] HU Y, HUANG H, JIANGY, et al. Liraglutide improves sevoflurane-induced postoperative cognitive dysfunction via activating autophagy and inhibiting apoptosis[J]. Aging (Albany NY), 2024, 16(4): 3763-3772.
[23] WUWF, CHEN C, LIN JT, et al.Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction[J]. Cell Mol Biol Lett, 2024, 29(1): 79.
[24] LU Z, WANG H, ISHFAQ M, et al.Quercetin and AMPK: A Dynamic Duo in Alleviating MG-Induced Inflammation via the AMPK/SIRT1/NF-κB Pathway[J]. Molecules, 2023, 28(21): 7388.
[25] XIE W, SUN J, ZHENG J, et al.Energy intake restriction significantly improves POCD after internal fixation of tibial fractures in mice[J]. Am J Transl Res, 2023, 15(3): 1667-1679.
[26] YANG LH, XU YC, ZHANG W.Neuroprotective effect of CTRP3 overexpression against sevoflurane anesthesia-induced cognitive dysfunction in aged rats through activating AMPK/SIRT1 and PI3K/AKT signaling pathways[J]. Eur Rev Med Pharmacol Sci, 2020, 24(9): 5091-5100.
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