背景:溃疡性结肠炎(UC),正在进行的结肠炎症性疾病,其特征是持续的粘膜表面刺激从直肠延伸到近端结肠。Tiron是维生素E的合成类似物,已知在各种动物模型中具有抗氧化和抗炎作用,因此,这项研究的目的是找出Tiron是否对乙酸引起的UC有任何预防性影响(A.A)大鼠暴露。
方法:腹膜内给药Tiron(235和470mg/kg)2周,和A.A(2毫升,3%v/v)直肠内注射引起结肠炎。然后收集结肠组织和血液样品用于测量各种炎症和氧化应激生物标志物。
结果:Tiron给药显著降低乳酸脱氢酶(LDH),C反应蛋白(CRP),结肠重量,和与A.A注射大鼠相比的结肠重量/长度比。此外,Tiron减弱氧化应激生物标志物。Tiron还强制胰高血糖素样肽-1(GLP-1)和三叶因子-3(TFF-3)的水平,同时大大降低了核因子κB(NF-κB)的表达,白细胞介素-6(IL-6),干扰素-γ(IFN-γ),和转化生长因子-1(TGF-β1),磷酸化表皮生长因子受体(P-EGFR),磷脂酰肌醇-3-激酶(PI3K)和蛋白激酶B(AKT)在结肠细胞结构中的表达。此外,结肠化学病理学损害,苏木精和曙红(H&E)和阿尔辛蓝染色显示,在Tiron给药后显著降低。
结论:Tiron通过调节炎症通路TGF-β1/P-EGFR/PI3K/AKT/NF-κB预防A.A.在管理氧化剂/抗氧化剂平衡的同时,提高肠屏障的可靠性。
BACKGROUND: Ulcerative colitis (UC), an ongoing inflammatory disorder of the colon, is marked by persistent mucosal surface irritation extending from the rectum to the near-proximal colon. Tiron is a synthetic analogue of vitamin E which is known to have antioxidant and anti-inflammatory effects in various animal models, so the goal of this study was to find out whether Tiron had any preventive impacts on UC inflicted by acetic acid (A.A) exposure in rats.
METHODS: Tiron (235 and 470 mg/kg) was administered intra-peritoneally for 2 weeks, and A.A (2 ml, 3 % v/v) was injected intra-rectally to cause colitis. Colon tissues and blood samples were then collected for measurement of various inflammatory and oxidative stress biomarkers.
RESULTS: Tiron administration significantly diminished lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon as compared to A.A-injected rats. Additionally, Tiron attenuated oxidative stress biomarkers. Tiron also enforced the levels of Glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3), while it greatly lowered the expression of nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interferon-γ (IFN-γ), and transforming growth factor-1(TGF-β1), phosphorylated epidermal growth factor receptor (P-EGFR), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) expression in colonic cellular structures. Furthermore, colonichistopathologic damages, revealed by hematoxylin and eosin (H&E) and Alcian Blue stain, were significantly decreased upon Tiron administration.
CONCLUSIONS: Tiron prevented A.A-induced colitis in rats via modulating inflammatory pathway TGF-β1/P-EGFR/PI3K/AKT/NF-κB, alongside managing the oxidant/antioxidant equilibrium, and boosting the reliability of the intestinal barrier.