溃疡性结肠炎对帕金森病的影响：肠道炎症、屏障功能损伤与神经炎症的研究
Impact of Ulcerative Colitis on Parkinson’s Disease: A Study on Gut Inflammation, Barrier Dysfunction, and Neuroinflammation

目的：本研究旨在探讨溃疡性结肠炎(Ulcerative Colitis, UC)是否通过肠道–脑轴机制加重帕金森病(Parkinson’s Disease, PD)的神经病理表现，并揭示肠道炎症及屏障损伤在其中的潜在作用机制。方法：将7周龄SPF级C57BL/6J雄性小鼠随机分为四组：对照组(CON组)、结肠炎组(DSS组)、PD模型组(MPTP组)、联合模型组(MPTP + DSS组)，每组6只。小鼠适应性饲养一周后进行以下处理：CON组腹腔注射生理盐水5天并持续饲养生理盐水；DSS组腹腔注射生理盐水5天，饲养21天后用2.5%葡聚糖硫酸盐(DSS)溶液诱导结肠炎；MPTP组腹腔注射30 mg/kg 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP) 5天并持续饲养28天以建立PD模型；MPTP + DSS组同样腹腔注射MPTP 5天，饲养21天后用2.5% DSS溶液诱导结肠炎。收集小鼠组织，利用高效液相色谱(HPLC)检测纹状体多巴胺(DA)水平；通过实时荧光定量PCR (RT-qPCR)检测结肠和黑质的炎症因子表达水平以及结肠紧密连接蛋白水平。结果：与MPTP组相比，MPTP + DSS组小鼠的纹状体DA水平显著降低(P < 0.05)，黑质炎症因子(IL-1β, IL-6, IL-8, TNF-α)表达显著升高(P < 0.05)。结论：本研究表明，溃疡性结肠炎通过破坏肠道屏障并激活肠–脑轴的炎症反应，进一步降低了PD小鼠纹状体DA水平，并增加黑质炎症因子的表达，从而加重了PD小鼠的神经损伤。
Objective: This study aimed to investigate whether ulcerative colitis (UC) exacerbates the neuropathological features of Parkinson’s disease (PD) through the gut-brain axis and to explore the potential role of intestinal inflammation and barrier disruption in this process. Methods: Seven-week-old SPF-grade male C57BL/6J mice were randomly divided into four groups: control (CON), DSS-induced colitis (DSS), PD model (MPTP), and combined model (MPTP + DSS), with six mice in each group. After one week of adaptive feeding, the mice were treated as follows: the CON group received intraperitoneal injections of normal saline for 5 days and continued on a normal saline diet; the DSS group received intraperitoneal injections of normal saline for 5 days, followed by 2.5% dextran sulfate sodium (DSS) solution to induce colitis after 21 days of normal feeding; the MPTP group received intraperitoneal injections of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 days and were fed normally for 28 days to establish a PD model; the MPTP + DSS group received MPTP injections for 5 days, followed by 2.5% DSS solution to induce colitis after 21 days of recovery. Tissue samples were collected, and striatal dopamine (DA) levels were measured using high-performance liquid chromatography (HPLC). Inflammatory cytokines in the colon and substantia nigra, as well as tight junction protein levels in the colon, were detected using real-time quantitative PCR (RT-qPCR). Results: Compared to the MPTP group, mice in the MPTP + DSS group exhibited significantly decreased striatal DA levels (P < 0.05) and significantly increased expression levels of inflammatory cytokines (IL-1β, IL-6, IL-8,