替罗尼改善乙酸诱导的大鼠结肠炎:TGF-β/EGFR/PI3K/NF-κB 信号通路的作用。
Tiron ameliorates acetic acid-induced colitis in rats: Role of TGF-β/EGFR/PI3K/NF-κB signaling pathway.
机构信息
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
出版信息
Int Immunopharmacol. 2024 Feb 15;128:111587. doi: 10.1016/j.intimp.2024.111587. Epub 2024 Jan 28.
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.
METHOD
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.
CONCLUSION
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.
背景
溃疡性结肠炎(UC)是一种持续性结肠炎症疾病,其特征为从直肠延伸至近端结肠的持续性黏膜表面刺激。Tiron 是维生素 E 的合成类似物,在各种动物模型中具有抗氧化和抗炎作用,因此本研究的目的是确定 Tiron 是否对乙酸(A.A)暴露诱导的大鼠 UC 具有预防作用。
方法
Tiron(235 和 470mg/kg)通过腹腔内给药 2 周,并用 A.A(2ml,3%v/v)直肠内注射以引发结肠炎。然后收集结肠组织和血液样本,以测量各种炎症和氧化应激生物标志物。
结果
与 A.A 注射大鼠相比,Tiron 给药可显著降低乳酸脱氢酶(LDH)、C 反应蛋白(CRP)、结肠重量和结肠重量/长度比。此外,Tiron 减轻了氧化应激生物标志物。Tiron 还增强了胰高血糖素样肽-1(GLP-1)和三叶因子-3(TFF-3)的水平,同时降低了核因子 kappa B(NF-κB)、白细胞介素-6(IL-6)、干扰素-γ(IFN-γ)和转化生长因子-β1(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,通过苏木精和伊红(H&E)和阿尔辛蓝染色显示,Tiron 给药显著降低了结肠组织病理学损伤。
结论
Tiron 通过调节 TGF-β1/P-EGFR/PI3K/AKT/NF-κB 炎症途径,同时管理氧化应激/抗氧化平衡,并增强肠道屏障的可靠性,预防 A.A 诱导的大鼠结肠炎。