骶骨上脊髓损伤后大鼠膀胱组织花生四烯酸代谢和功能变化的时间依赖性。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-10-17 DOI:10.1016/j.expneurol.2024.114989

Yi Rong , Yinbo Kang , Jie Wen , Qian Gong , Wenlong Zhang , Ke Sun , Weibing Shuang

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引用次数: 0

摘要

背景：影响创伤性脊髓损伤（TSCI）患者生活质量的一个重要方面是膀胱功能障碍。花生四烯酸的代谢是参与无数生理过程的重要脂质信号分子。在这项研究中，我们首次使用二十碳六烯酸代谢组学检测逼尿肌收缩，以评估花生四烯酸代谢对 TSCI 后膀胱功能障碍的影响。此外，我们还探讨了膀胱组织炎症和功能变化的时间：方法：对成年雄性 Sprague-Dawley 大鼠进行改良体重下降法手术。方法：对成年雄性 Sprague-Dawley 大鼠进行改良负重法手术，并进行逼尿肌收缩检查、尿动力学检查、类二十烷代谢组学、透射电子显微镜、Elisa 和组织学染色，以评估 TSCI 术后炎症、代谢和功能变化的时间变化：结果：TSCI 后，在膀胱功能变化之前，膀胱组织发生了炎症变化，包括炎症因子增加、线粒体损伤和轻微脂质过氧化。随着时间的推移，炎症变化逐渐减轻。然而，从 TSCI 后的第三天开始，膀胱组织出现了继发性病变。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加剧，而且逼尿肌收缩力也开始发生显著变化。我们还发现，花生四烯酸代谢途径中代谢产物的含量与排尿肌收缩力的变化程度有很强的相关性。此外，我们还发现大鼠在 TSCI 后的第七天已经度过了脊髓休克期：总之，我们首次证明花生四烯酸代谢异常在 TSCI 后膀胱功能障碍中扮演了重要角色。我们还证明，3d 是大鼠膀胱组织发生变化的关键时刻，这表明它是治疗神经源性膀胱的重要关头。

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Time-dependent arachidonic acid metabolism and functional changes in rats bladder tissue after suprasacral spinal cord injury

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.