The First Hospital of Shanxi Medical University, Jiefang Rd, Shanxi 030000, China; First Clinical Medical College, Shanxi Medical University, Jiefang Rd, Shanxi 030000, China.
The First Hospital of Shanxi Medical University, Jiefang Rd, Shanxi 030000, China.
Exp Neurol. 2025 Jan;383:114989. doi: 10.1016/j.expneurol.2024.114989. Epub 2024 Oct 17.
A critical aspect affecting the quality of life in Traumatic spinal cord injury (TSCI) patients is bladder dysfunction. Metabolities in arachidonic acid are crucial lipid signaling molecules involved innumerous physiological processes. In this study, We are the first use eicosanoid metabolomics detrusor contraction examine, to assess the effect of the arachidonic acid metabolic in bladder dysfunction following TSCI. In additon, we explore the time of inflammatory and function changes in bladder tissue.
Adult male Sprague-Dawley rats were subjected to improved Weight Drop method surgeries. Detrusor contraction examination, urodynamic examination, eicosanoid metabolomics, transmission electron microscopy, Elisa and histological staining were performed to assess the change of inflammatory, metabolic and function variation over time after TSCI.
Following TSCI, before the variations of bladder function, inflammatory changes including the increase of inflammatory factors, mitochondrial damage, and slight lipid peroxidation, occurred in bladder tissue. And the inflammatory changes gradually decreases over time. However, From the third day after TSCI, secondary lesions appeared in bladder tissue. Not only did inflammation-related indexes increase again, the degree of mitochondrial damage and lipid peroxidation increased, but also the contractility of detrusor began to change significantly. We also found that the content of metabolites in arachidonic acid metabolic pathway and the degree of detrusor contractility change showed a strong correlation. In addition, we found that rats had moved beyond the spinal shock stage on the seventh day after TSCI.
Altogether, we are the first to demonstrate that abnormal arachidonic acid metabolism plays an important role in bladder dysfunction after TSCI. We also demonstrate that 3d is a critical juncture for changes in rat bladder tissue, which indicates it is an important juncture in the treatment of neurogenic bladder.
影响创伤性脊髓损伤(TSCI)患者生活质量的一个关键方面是膀胱功能障碍。花生四烯酸代谢物是参与许多生理过程的重要脂质信号分子。在这项研究中,我们首次使用花生四烯酸代谢组学检测逼尿肌收缩,评估 TSCI 后膀胱功能障碍中花生四烯酸代谢的影响。此外,我们还探讨了膀胱组织中炎症和功能变化的时间。
成年雄性 Sprague-Dawley 大鼠接受改良重物坠落法手术。进行逼尿肌收缩检查、尿动力学检查、花生四烯酸代谢组学、透射电镜、Elisa 和组织学染色,以评估 TSCI 后炎症、代谢和功能变化随时间的变化。
TSCI 后,在膀胱功能变化之前,膀胱组织中出现炎症变化,包括炎症因子增加、线粒体损伤和轻微脂质过氧化。并且炎症变化随时间逐渐减少。然而,从 TSCI 后第三天开始,膀胱组织出现继发性病变。不仅炎症相关指标再次增加,线粒体损伤和脂质过氧化程度增加,而且逼尿肌的收缩性也开始发生显著变化。我们还发现,花生四烯酸代谢途径中的代谢物含量和逼尿肌收缩性变化的程度呈强相关性。此外,我们发现大鼠在 TSCI 后第七天已经超过了脊髓休克阶段。
总之,我们首次证明异常的花生四烯酸代谢在 TSCI 后膀胱功能障碍中起重要作用。我们还证明 3d 是大鼠膀胱组织变化的关键节点,这表明它是治疗神经源性膀胱的重要节点。