背景:石榴籽油(PSO)和鳄梨籽油(ASO)是具有既定抗炎活性的天然多酚。
目的:本研究旨在探讨PSO和ASO治疗实验性溃疡性结肠炎(UC)的分子机制。
方法:80只雄性白化病大鼠,PSO,ASO,SLZ,UC控制,(UC+PSO),(UC+ASO)和(UC+SLZ)组。通过直肠内注射乙酸诱发结肠炎。PSO(0.5ml/200g),ASO(1ml/250g)和SLZ(100mg/kg)口服1次/天,连续14天,结肠炎诱导后24h。通过测量疾病活动指数(DAI)评估结肠炎,结肠重量/长度比和组织学炎症评分。血管内皮生长因子受体-2(VEGFR-2),结肠巨噬细胞移动抑制因子(MIF),测定丙二醛(MDA)含量。结肠基因表达TNF-α,还估计了VEGF和血红素加氧酶-1(HO-1)。
结果:PSO和ASO治疗UC大鼠显著降低DAI,重量/长度比,VEGFR-2和结肠组织学炎症评分与UC对照。ASO比PSO显著抑制MIF水平和TNF-α表达。然而,PSO在降低MDA水平和上调HO-1表达方面比ASO更显著。两种油均显著下调VEGF表达。所获得的UC诱导的生化和组织学变化几乎被SLZ纠正。
结论:已证明PSO和ASO作为抗炎的有益作用,抗血管生成,UC大鼠的抗氧化作用可能通过抑制TNF-α介导,VEGF,和MIF和HO-1的上调。
BACKGROUND: Pomegranate seed oil (PSO) and avocado seed oil (ASO) are natural polyphenols with established anti-inflammatory activity.
OBJECTIVE: This study aimed to investigate the molecular mechanisms underlying the therapeutic efficacy of PSO and ASO in experimental ulcerative colitis (UC) with reference to sulfasalazine (SLZ).
METHODS: Eighty male albino rats were divided equally into 8 groups; Normal, PSO, ASO, SLZ, UC-control, (UC + PSO), (UC + ASO) and (UC + SLZ) groups. Colitis was induced by intra-rectal injection of acetic acid. PSO (0.5ml/200g), ASO (1ml/250g) and SLZ (100 mg/kg) were administered orally once/day for 14 days, 24h after colitis induction. Colitis was evaluated by measuring disease activity index (DAI), colon weight/length ratio and histologic inflammatory score. Vascular endothelial growth factor receptor-2 (VEGFR-2), colonic macrophage migration inhibitory factor (MIF), and malondialdehyde (MDA) were determined. Colonic gene expression of TNF-α, VEGF and heme oxygenase-1 (HO-1) were also estimated.
RESULTS: PSO and ASO treatments to UC rats significantly reduced DAI, weight/length ratio, VEGFR-2, and colon histologic inflammatory score versus UC-controls. ASO significantly suppressed MIF levels and TNF-α expression greater than PSO. However, PSO was more significant than ASO in reducing MDA levels and up-regulating HO-1 expression. Both oils significantly down-regulated VEGF expression. The obtained biochemical and histological changes induced by UC were nearly corrected by SLZ.
CONCLUSIONS: The proved beneficial effect of PSO and ASO as anti-inflammatory, anti-angiogenic, and antioxidant in UC rats could be mediated by suppression of TNF-α, VEGF, and MIF and up-regulation of HO-1.