牙髓干细胞与柳氮磺胺吡啶联合干预溃疡性结肠炎大鼠模型。
Combinatorial intervention with dental pulp stem cells and sulfasalazine in a rat model of ulcerative colitis.
机构信息
Basic Dental Science Department, Oral & Dental Research Institute, National Research Centre, 33 El Bohouth St, Dokki, Giza, Egypt.
Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt.
出版信息
Inflammopharmacology. 2024 Dec;32(6):3863-3879. doi: 10.1007/s10787-024-01532-w. Epub 2024 Jul 29.
BACKGROUND
Ulcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo.
METHODS
Ulcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue.
RESULTS
The investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression.
CONCLUSIONS
Cotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved.
背景
溃疡性结肠炎是一种炎症性肠病（IBD），涉及结肠内层和直肠的炎症。虽然尚未确定 IBD 的明确治疗方法，但已经提出了各种治疗方法来减轻这种疾病的症状表现，主要侧重于减轻炎症。本研究旨在评估将牙髓干细胞（DPSCs）与柳氮磺胺吡啶联合应用于乙酸诱导的溃疡性结肠炎大鼠模型中的治疗潜力，并评估这种联合用药对体内抑制炎症细胞因子和调节氧化应激的影响。
方法
通过直肠内给予 3%乙酸诱导大鼠溃疡性结肠炎。通过测量结肠重量/长度比和水肿标志物；对结肠组织进行组织病理学检查；对 NF-κB-P65 和 IL-1β进行免疫组织化学染色；通过 ELISA 评估氧化应激和抗氧化指标；此外，通过 ELISA 评估结肠组织中的促炎标志物 NF-κB-P65、TNF-α 和 TLR-4。此外，通过 qRT-PCR 估计结肠组织中 TLR-4、NF-κB-P65 和 MYD88 基因的表达水平。
结果
联合使用柳氮磺胺吡啶和 DPSCs 后，观察到炎症的宏观和微观表现明显改善，组织学结构明显改善，黏膜上皮完整，黏膜和黏膜下层轻度炎症浸润，仅有轻微出血。单独或联合使用 DPSCs 或柳氮磺胺吡啶均可显著降低 ROS 水平并显著增加 XOD 活性。免疫组织化学结果表明，联合使用 DPSCs 和柳氮磺胺吡啶可减轻 NFκB-p65 和 IL-1β 的表达。最后，联合使用 DPSCs 和柳氮磺胺吡啶可显著下调 MyD88、NF-κB 和 TLR4 基因表达。
结论
DPSCs 和柳氮磺胺吡啶联合治疗溃疡性结肠炎具有协同作用，可缓解疾病。
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