Tamer Sevil Arabacı, Köse Fadime, Yanar Sevinç, Budak Özcan, Bağcı Cahit
Department of Physiology, School of Medicine, Sakarya University, Sakarya, Türkiye.
Department of Histology and Embryology, School of Medicine, Sakarya University, Sakarya, Türkiye.
J Biochem Mol Toxicol. 2025 May;39(5):e70285. doi: 10.1002/jbt.70285.
Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation and ulcers in the lining of the colon and rectum. Spexin is a novel peptide with antioxidant and anti-inflammatory properties. This study aims to elucidate the therapeutic effects and underlying mechanisms of spexin in mitigating acetic acid-induced colitis in rats. Male Sprague Dawley rats were assigned to control (n = 14) and colitis (n = 21) groups. Colitis was induced via 5% acetic acid (AA) administration (1 mL, intrarect). Post-induction, rats received subcutaneous saline (1 mL/kg), spexin (50 µg/kg/day), or oral sulfasalazine (500 mg/kg) for 5 days. Control groups received saline or spexin. After 24 h of the final treatment, colons were evaluated macroscopically, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18 were determined by ELISA, oxidative stress markers myeloperoxidase (MPO), malondialdehyde (MDA) and glutathione (GSH) levels were measured spectrophotometrically and NOD-like receptor pyrin domain-containing 3 (NLRP3), nuclear factor-κB (NF-κB), caspase-1 proteins were analyzed with Western Blot alongside histopathological assessments. Colitis induction significantly elevated macroscopic damage scores, stool consistency, inflammatory cytokines, MDA, MPO, and NLRP3, NF-κB, caspase-1, while reducing GSH levels (p < 0.001-0.01). Microscopic evaluations confirmed increased necrosis, submucosal edema, and inflammatory cell infiltration (p < 0.001). Spexin reversed these effects by enhancing GSH levels (p < 0.01), reducing macroscopic/microscopic scores, cytokines, MDA, and MPO levels (p < 0.05-0.001), and suppressing NLRP3, NF-κB, and caspase-1 activation (p < 0.01-0.001). For the first time that spexin ameluates acetic acid-induced colitis in rats by modulating the NF-κB/NLRP3 signaling pathway, reducing oxidative damage, enhancing antioxidant capacity, and suppressing inflammation.
溃疡性结肠炎是一种慢性炎症性肠病，其特征为结肠和直肠黏膜的炎症和溃疡。Spexin是一种具有抗氧化和抗炎特性的新型肽。本研究旨在阐明Spexin减轻大鼠乙酸诱导的结肠炎的治疗效果及潜在机制。将雄性Sprague Dawley大鼠分为对照组（n = 14）和结肠炎组（n = 21）。通过直肠内给予5%乙酸（AA，1 mL）诱导结肠炎。诱导后，大鼠皮下注射生理盐水（1 mL/kg）、Spexin（50 μg/kg/天）或口服柳氮磺胺吡啶（500 mg/kg），持续5天。对照组接受生理盐水或Spexin。在最后一次治疗24小时后，对结肠进行宏观评估，通过酶联免疫吸附测定法测定肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-18水平，用分光光度法测量氧化应激标志物髓过氧化物酶（MPO）、丙二醛（MDA）和谷胱甘肽（GSH）水平，并用蛋白质免疫印迹法分析含NOD样受体吡咯结构域蛋白3（NLRP3）、核因子-κB（NF-κB）、半胱天冬酶-1蛋白，同时进行组织病理学评估。结肠炎诱导显著提高了宏观损伤评分、粪便稠度、炎性细胞因子、MDA、MPO以及NLRP3、NF-κB、半胱天冬酶-1水平，同时降低了GSH水平（p < 0.001 - 0.01）。微观评估证实坏死增加、黏膜下水肿和炎性细胞浸润（p < 0.001）。Spexin通过提高GSH水平（p < 0.01）、降低宏观/微观评分、细胞因子、MDA和MPO水平（p < 0.05 - 0.001）以及抑制NLRP3、NF-κB和半胱天冬酶-1的激活（p < 0.01 - 0.001）逆转了这些效应。首次发现Spexin通过调节NF-κB/NLRP3信号通路、减少氧化损伤、增强抗氧化能力和抑制炎症来改善大鼠乙酸诱导的结肠炎。
