膝关节骨性关节炎晚期患者血细胞中的高糖酵解率和氧化与磷酸化解偶联活性与术后疼痛发生的关系

E. B. Chetina, G. A. Markova, K. E. Glemba, M. Makarov
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摘要

目的:研究骨关节炎(OA)患者全膝关节置换术(TKA)后,介导细胞能量产生的基因表达与慢性术后疼痛(CPP)发生之间的关系。在进行全膝关节置换术之前,对 50 名患有 III-IV 期膝 OA 并主诉持续疼痛和关节功能障碍的患者的血液进行了分析。对照组由 26 名健康人组成。疼痛强度通过视觉模拟量表(VAS)、BPI短问卷和WOMAC指数进行评估,神经性疼痛通过DN4和PainDETECT问卷进行评估。TKA术后3个月和6个月测定CPP的发展情况。通过实时定量反转录聚合酶链反应,从血液中分离出的总 RNA 被用于检测 PKM2、LDH、SDH、AMPKα、PDH、IDH、MDH 和 ATP 合成酶基因的表达。17例患者的VAS显示CPP≥30 mm。与对照组相比,TKA前所有分析基因的表达均明显增加。然而,在分析的 OA 患者组中,临床、疼痛相关指标和功能指标均无差异。手术前,与糖酵解(PKM2、LDH)、克雷布斯循环-KC(SDH)和能量代谢主调节因子(AMPKα)相关的基因表达量明显高于对 TKA 术后效果满意的患者。同时,PDH 和其他 KC 酶基因(IDH、MDH)以及 ATP 合酶的表达在 CPP 患者和非 CPP 患者中没有发现差异。CPP的发生与较高的糖酵解率和能量缺乏有关,这可能是由于在TKA之前可以观察到较高的氧化和磷酸化解偶联活性。
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Association of a high rate of glycolysis and the activity of the uncoupling of oxidation and phosphorylation in the blood cells of patients with late-stage knee osteoarthritis and the development of postoperative pain
Objective: to investigate the relationship between the expression of genes mediating cellular energy production and the development of chronic postoperative pain (CPP) after total knee arthroplasty (TKA) in patients with osteoarthritis (OA).Material and methods. Prior to TKA, the blood of 50 patients with stage III–IV knee OA and complaints of constant pain and joint dysfunction was analyzed. The control group consisted of 26 healthy individuals. Pain intensity was assessed using a visual analogue scale (VAS), a short BPI questionnaire and the WOMAC index, and the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of CPP was determined 3 and 6 months after TKA. Total RNA isolated from blood was used to determine the expression of PKM2, LDH, SDH, AMPKα, PDH, IDH, MDH and ATP synthase genes by real-time quantitative reverse transcriptase-polymerase chain reaction.Results and discussion. CPP ≥30 mm according to VAS was detected in 17 patients. Before TKA, the expression of all analyzed genes was significantly increased compared to that of the control group. However, there were no differences in clinical, pain-related and functional indicators in the analyzed group of patients with OA. Before surgery, patients who subsequently developed CPP had significantly higher expression of genes related to glycolysis (PKM2, LDH), Krebs cycle – KC (SDH) and master regulator of energy metabolism (AMPKα) than patients who were satisfied with the results of TKA. At the same time, no differences were found in the expression of PDH and other KC enzyme genes (IDH, MDH) and ATP synthase in patients with and without CPP.Conclusion. The development of CPP is associated with a higher rate of glycolysis and energy deficiency, presumably due to the higher uncoupling activity of oxidation and phosphorylation that can be observed before TKA.
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