Department of Urology, The Third Affiliated Hospital and Lingnan Hospital of the Sun Yat-Sen University, 2693 Kaichuang Road, Guangzhou 510700, China.
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong, China.
Life Sci. 2023 Oct 15;331:122045. doi: 10.1016/j.lfs.2023.122045. Epub 2023 Aug 25.
Neuroinflammation in the spinal dorsal horn (SDH) region plays an important role in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). Oxidative stress is an important etiological factor for inflammatory diseases. This study aimed to investigate the therapeutic effects of umbilical cord mesenchymal stem cells UMSCs on neuroinflammation and oxidative stress in IC and the underlying mechanisms.
Rats were intraperitoneally injected with cyclophosphamide (50 mg/kg bodyweight) to establish the IC animal model. Additionally, rats were intrathecally injected with a Sirt1-specific agonist (SRT1720; 8 μg/rat) or inhibitor (EX527; 8 μg/rat). Furthermore, rats were intrathecally injected with human UMSCs (hUMSCS; 8 × 10 cells/rat). Rat behavior was examined using the mechanical allodynia test, novel object recognition test, sucrose preference test, and urodynamics analysis. Neuroinflammation and oxidative stress the SDH region were examined using western blotting, immunofluorescence, enzyme-linked immunosorbent assay, and commercial kits.
The Sirt1/Nrf2/HO-1 pathway was downregulated in IC rats. Sirt1 activation and inhibition differentially affected the behavior of IC rats. hUMSCs effectively mitigated the upregulation of oxidative stress, proinflammatory cytokines, and glial activation in the SDH region. Additionally, hUMSCs suppressed mechanical allodynia, dysregulated urodynamics, memory deficits, and depressive-like behavior in IC rats. hUMSCs exerted therapeutic effects through the Sirt1/Nrf2/HO-1 pathway.
intrathecal hUMSCs injection alleviated behavioral deficits of IC rats by mitigating neuroinflammation and oxidative stress through the Sirt1/Nrf2/HO-1 pathway and can be potentially an effective therapeutic strategy for IC.
脊髓背角（SDH）区域的神经炎症在间质性膀胱炎（IC）/膀胱疼痛综合征（BPS）的发病机制中起重要作用。氧化应激是炎症性疾病的一个重要病因。本研究旨在探讨脐带间充质干细胞（UMSC）对 IC 中神经炎症和氧化应激的治疗作用及其潜在机制。
通过腹腔注射环磷酰胺（50mg/kg 体重）建立 IC 动物模型。此外，通过鞘内注射 Sirt1 特异性激动剂（SRT1720；8μg/大鼠）或抑制剂（EX527；8μg/大鼠）。进一步，通过鞘内注射人 UMSC（hUMSC；8×10 细胞/大鼠）。使用机械性痛觉过敏试验、新物体识别试验、蔗糖偏好试验和尿动力学分析检查大鼠行为。使用 Western blot、免疫荧光、酶联免疫吸附试验和商业试剂盒检测 SDH 区域的神经炎症和氧化应激。
Sirt1/Nrf2/HO-1 通路在 IC 大鼠中下调。Sirt1 激活和抑制对 IC 大鼠的行为有不同的影响。hUMSC 有效减轻 SDH 区域氧化应激、促炎细胞因子和神经胶质激活的上调。此外，hUMSC 抑制 IC 大鼠的机械性痛觉过敏、失调的尿动力学、记忆缺陷和抑郁样行为。hUMSC 通过 Sirt1/Nrf2/HO-1 通路发挥治疗作用。
鞘内注射 hUMSC 通过 Sirt1/Nrf2/HO-1 通路减轻 IC 大鼠的行为缺陷，减轻神经炎症和氧化应激，可能是 IC 的一种有效治疗策略。
