Yu Zhen, Wang Xianfeng, Hu Yusen, Wang Xinfa, Zhu Zhenghuan, Xu Xu, Wang Yiming, Zhang Ailiang
Department of Articular Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Department of Orthopedic Surgery, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, China.
Balkan Med J. 2025 Jan 2;42(1):27-36. doi: 10.4274/balkanmedj.galenos.2024.2024-7-92.
Previous research has shown that apoptosis of nucleus pulposus (NP) cells contributes to intervertebral disc degeneration (IDD) progression. Endoplasmic reticulum (ER) stress is a reaction to diverse stimuli in eukaryotes and is tightly contacted with apoptosis. Quercetin, a naturally occurring flavonoid, exerts protective effects against degenerative diseases via ER stress. However, the effect of quercetin on NP cell apoptosis remains unclear.
To investigate the influences of quercetin on apoptosis and ER stress in a high-glucose-generated primary NP cell model.
In vivo animal experimental study.
To investigate the influence of quercetin in a high-glucose-generated NP cell apoptosis model, control, glucose, and glucose + quercetin groups adopted with Sprague-Dawley rats primary NP cells. In the glucose group, cell apoptosis was generated by 200 mm high glucose. In the glucose + quercetin group, 60 μm quercetin was pretreated with NP cells for 2 h before glucose administration. In this research, we examined the change effect of quercetin on NP cell apoptosis, ER stress, and the protein kinase R-like ER kinase (PERK)-eukaryotic translation initiation element 2α (eIF2α)-activating transcription element 4 (ATF4).
High glucose decreased the viability and induced ER stress-related apoptosis in NP cells. Quercetin modulated ER stress through the PERK-eIF2α-ATF4 pathway, thereby alleviating the apoptosis rank in NP cells.
Quercetin exerts antiapoptotic effects on NP cells, probably through ER stress, thereby showcasing potential as a therapeutic method for treating IDD.
先前的研究表明,髓核(NP)细胞凋亡会促进椎间盘退变(IDD)的进展。内质网(ER)应激是真核生物对多种刺激的一种反应,且与细胞凋亡密切相关。槲皮素是一种天然存在的黄酮类化合物,可通过内质网应激对退行性疾病发挥保护作用。然而,槲皮素对NP细胞凋亡的影响仍不清楚。
研究槲皮素对高糖诱导的原代NP细胞模型中细胞凋亡和内质网应激的影响。
体内动物实验研究。
为研究槲皮素在高糖诱导的NP细胞凋亡模型中的作用,将Sprague-Dawley大鼠原代NP细胞分为对照组、葡萄糖组和葡萄糖+槲皮素组。葡萄糖组中,用200 mM高糖诱导细胞凋亡。葡萄糖+槲皮素组中,在给予葡萄糖前,先用60 μM槲皮素预处理NP细胞2小时。本研究检测了槲皮素对NP细胞凋亡、内质网应激以及蛋白激酶R样内质网激酶(PERK)-真核翻译起始因子2α(eIF2α)-激活转录因子4(ATF4)的变化影响。
高糖降低了NP细胞的活力并诱导内质网应激相关的细胞凋亡。槲皮素通过PERK-eIF2α-ATF4通路调节内质网应激,从而减轻NP细胞的凋亡程度。
槲皮素可能通过内质网应激对NP细胞发挥抗凋亡作用,从而展现出作为治疗IDD的一种治疗方法的潜力。