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.
方法:经直肠给药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来评估DPSC和柳氮磺胺吡啶联合对UC的治疗效果;进行结肠组织病理学检查;对NF-κB-P65和IL-1β进行免疫组织化学染色;并通过ELISA评估氧化应激和抗氧化指标。此外,用ELISA法检测结肠组织中的促炎标志物NF-κB-P65、TNF-α和TLR-4。此外,qRT-PCR用于评估TLR-4、NF-κB-P65和MYD88基因在结肠组织中的表达水平。
结果:柳氮磺吡啶和DPSC联合给药后,所研究的炎症的宏观和微观征象得到了明显改善,组织学结构明显改善,粘膜上皮完整,粘膜和粘膜下层有轻度炎症浸润,轻微出血.DPSC或柳氮磺胺吡啶的给药,无论是单独还是组合,显著降低ROS水平和显著增加XOD活性。免疫组织化学结果表明,DPSC和柳氮磺胺吡啶的联合给药降低了NFκB-p65和IL-1β的表达。最后,DPSC和柳氮磺胺吡啶联合给药显著下调MyD88、NF-κB和TLR4基因表达。
结论:DPSC和柳氮磺胺吡啶协同治疗溃疡性结肠炎,这些影响得到了缓解。