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腰骶部脊髓狭窄、生活方式因素和血糖失调对神经营养因子表达的调节作用

Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation.

作者信息

Sobańska Małgorzata, Sobański Dawid, Staszkiewicz Rafał, Gogol Paweł, Strojny Damian, Pawłaszek Tomasz, Dammerman Werner, Grabarek Beniamin Oskar

机构信息

Department of Neurosurgery, Szpital sw. Rafala in Cracow, 30-693 Cracow, Poland.

Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland.

出版信息

Biomedicines. 2025 May 1;13(5):1102. doi: 10.3390/biomedicines13051102.

Abstract

: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. : We analyzed mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. : NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels ( < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA = 0.032 for mRNA, = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, = 0.015) and diabetes (β = 0.39, = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association ( = 0.046), while smoking showed no significant independent effect. : Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation.

摘要

腰骶部椎管狭窄症(LSS)是一种退行性疾病,其特征为椎管狭窄及相关的神经性疼痛。虽然机械性压迫已得到充分研究,但导致症状严重程度的分子机制仍知之甚少。神经营养因子(NRTN)是胶质细胞源性神经营养因子家族的成员,已成为神经可塑性和伤害感受的潜在介质,但其在椎管狭窄中的作用在很大程度上尚未得到探索。

我们分析了96例接受LSS手术患者和85例非退行性尸检对照的黄韧带样本中的mRNA和蛋白表达。使用实时定量聚合酶链反应(RT-qPCR)、酶联免疫吸附测定(ELISA)、蛋白质印迹法和免疫组织化学进行定量分析。疼痛严重程度视觉模拟量表(VAS)、体重指数(BMI)、糖尿病、吸烟和饮酒情况被评估为NRTN表达的调节因素。

与对照组相比,LSS患者的NRTN在转录本和蛋白水平上均显著升高(<0.05)。NRTN水平与疼痛强度呈正相关(VAS;mRNA的方差分析P = 0.032,蛋白的P = 0.041)。多变量回归分析确定BMI(β = 0.50,P = 0.015)和糖尿病(β = 0.39,P = 0.017)是NRTN表达增加的独立预测因素。饮酒也显示出正相关(P = 0.046),而吸烟未显示出显著的独立影响。

神经营养因子在LSS患者的黄韧带组织中上调,且与疼痛严重程度和代谢风险因素相关。这些发现表明NRTN可能是退行性脊柱疾病的生物标志物和治疗靶点。有必要进行进一步的纵向和机制研究,以阐明其在慢性疼痛和神经炎症中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf81/12109087/5d5260467ead/biomedicines-13-01102-g001.jpg

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