山西医科大学学报2025，Vol.56Issue(4)：398-405,8.DOI:10.13753/j.issn.1007-6611.2025.04.008
艾司氯胺酮对大鼠软骨细胞增殖的影响及其机制
Effects of Esketamine on rat chondrocyte proliferation and its mechanism
摘要
Abstract
Objective To investigate the effects of Esketamine(Esket)on the proliferation of rat chondrocytes and its potential mecha-nism.Methods Chondrocytes were isolated from femoral heads of 4-week-old male SD rats and cultured.Second-passage chondro-cytes were treated with 0,12.5,25,50,100,200 μmol/L Esketamine or N-methyl-D-aspartate(NMDA)for 24,48,and 72 h,re-spectively.The non-toxic concentration ranges of Esket and NMDA on chondrocyte proliferation were determined using CCK-8 assay.Subsequently,second-passage chondrocytes were divided into three groups:control group,Esket group,and Esket+NMDA group.Af-ter 24,48,72 h intervention,mRNA and protein expression levels of protein kinase A(PKA),extracellular signal-regulated kinases 1/2(ERK1/2),and cyclic-AMP response element binding protein(CREB)were detected by quantitative real-time PCR(qRT-PCR)and ELISA,respectively.Results CCK-8 results showed 0-200 μmol/L Esketamine or NMDA had no significant cytotoxicity to chondrocytes.Compared with control group,PKA mRNA expression showed no statistically significant differences at 24 h,48 h,or 72 h in Esket group(P>0.05),while its protein expression was significantly upregulated at 48 h(P<0.05).Compared with Esket group,PKA protein expression was reduced at 48 h in Esket+NMDA group(P<0.05).At 48 h,ERK1/2 mRNA expression was significantly higher in Esket group than in control group(P<0.001),and it was lower in Esket+NMDA group than in Esket group(P<0.05).Compared with control group,CREB mRNA expression was increased at 24 h in Esket group(P<0.01),and CREB mRNA and protein expressions were increased at 48 h(P<0.05).Compared with Esket group,CREB mRNA expression was decreased at 24,48 h in Esket+NMDA group(P<0.05),and its protein expression was also decreased at 48 h(P<0.05).Conclusion Esketamine may promote rat chondro-cyte proliferation by antagonizing NMDA receptors and activating PKA-ERK1/2-CREB signaling pathway.关键词
艾司氯胺酮/NMDA/软骨细胞/细胞增殖/蛋白激酶A/细胞外信号调节酶1/2/cAMP反应元件结合蛋白Key words
Esketamine/NMDA/chondrocyte/cell proliferation/protein kinase A/extracellular signal-regulated kinase 1/2/cyclic-AMP response element binding protein分类
临床医学引用本文复制引用
李彪,张忠成,马智聪..艾司氯胺酮对大鼠软骨细胞增殖的影响及其机制[J].山西医科大学学报,2025,56(4):398-405,8.基金项目
山西省卫生健康委科研课题(2023023) （2023023）
