中国药房2025，Vol.36Issue(21)：2674-2680,7.DOI:10.6039/j.issn.1001-0408.2025.21.10
艾司氯胺酮通过AMPK/SIRT1/PGC-1α信号通路改善髋部骨折大鼠术后认知功能障碍的机制
Mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture through AMPK/SIRT1/PGC-1α signaling pathway
摘要
Abstract
OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase(AMPK)/silencing information regulatory factor 1(SIRT1)/peroxisome proliferator activated-receptor-γ coactivator-1α(PGC-1α)signaling pathway.METHODS Rats with hip fracture surgery were assigned into model group,esketamine group(10 mg/kg),inhibitor group(250 μg/mL AMPK inhibitor Compound C),and esketamine+inhibitor group(10 mg/kg esketamine+250 μg/mL Compound C),and rats undergoing sham surgery were used as the control group,with 12 rats in each group.New object recognition and Barnes maze experiments were used to evaluate cognitive function in rats.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),superoxide dismutase(SOD),malondialdehyde(MDA),gamma-aminobutyric acid(GABA),dopamine(DA)and glutamate(Glu),and the apoptosis of hippocampal neurons were detected.The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed.The mRNA expression of B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax),the mRNA and protein expression of AMPK,SIRT1 and PGC-1α,as well as the expression of phosphorylated(p)-AMPK in hippocampal tissue,were detected.RESULTS Compared with the control group,the hippocampal neurons in the model group of rats were disordered,with more neurons necrotic and swollen mitochondria;the new object recognition index,the SOD,GABA,DA levels,Bcl-2,AMPK,SIRT1 and PGC-1α mRNA expression levels,and p-AMPK,SIRT1,PGC-1α protein expression levels were significantly reduced,while the latency and number of errors for locating unknown holes,the TNF-α,IL-1β,MDA and Glu levels,neuronal cell apoptosis rate,and Bax mRNA expression levels were significantly increased/prolonged(P＜0.05).Compared with the model group,the esketamine group showed reduced pathological damage to the hippocampal tissue of rats,and the new object recognition index,the SOD,GABA and DA levels,the Bcl-2,AMPK,SIRT1 and PGC-1α mRNA expression levels,and p-AMPK,SIRT1,PGC-1α protein expression levels were significantly increased,while the latency and error frequency for locating unknown holes,TNF-α,IL-1β,MDA and Glu levels,neuronal cell apoptosis rate,and Bax mRNA expression levels were significantly decreased(P＜0.05);the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group(P＜0.05).AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats(P＜0.05).CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway,inhibiting neuronal cell apoptosis,improving mitochondrial structure,and promoting postoperative cognitive function recovery.关键词
艾司氯胺酮/AMP活化蛋白激酶/沉默信息调节因子1/过氧化物酶体增殖物激活受体γ共激活因子1α/髋部骨折/认知功能障碍Key words
esketamine/AMP-activated protein kinase/silencing information regulator factor 1/peroxisome proliferator activated receptor-γ coactivator-1α/hip fracture/cognitive impairment分类
临床医学引用本文复制引用
刘璇,张晓敏,刘进婷,郝岩,汪业铭,陈丽星..艾司氯胺酮通过AMPK/SIRT1/PGC-1α信号通路改善髋部骨折大鼠术后认知功能障碍的机制[J].中国药房,2025,36(21):2674-2680,7.基金项目
张家口市科技计划项目(No.2421055D) （No.2421055D）
