Department of Pediatric Gastroenterology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Bosn J Basic Med Sci. 2021 Feb 1;21(1):33-38. doi: 10.17305/bjbms.2020.4823.
Tumor necrosis factor-alpha (TNF-α) has an important role in hypoxia/reoxygenation (H/R)-induced intestinal damage. It was shown that blocking TNF-α with infliximab has beneficial effects on experimental necrotizing enterocolitis and hypoxic intestinal injury. However, there is no data about the effect of adalimumab on H/R-induced intestinal damage. Therefore, we aimed to determine potential dose-dependent benefits of adalimumab in such damage in neonatal rats. Wistar albino rat pups were assigned to one of the four groups: control group, hypoxia group, low-dose adalimumab (5 mg/kg/day) treated group (LDAT), and high-dose adalimumab (50 mg/kg/day) treated group (HDAT). On the fourth day of the experiment, all rats except for the control group were exposed to H/R followed by euthanasia. Malondialdehyde (MDA), myeloperoxidase (MPO), TNF-α, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured in intestinal tissue. TAC and TOC values were used to calculate the oxidative stress index (OSI). Histopathological injury scores (HIS) were also evaluated in the tissue samples. MDA levels were significantly lower in the LDAT and HDAT groups (p < 0.001). TNF-α levels were significantly lower in the LDAT group (p < 0.001). OSI was significantly higher in the H/R group than in the control and LDAT groups (p < 0.001). Mean HIS values in the LDAT group were significantly lower than those in the H/R and HDAT groups (p < 0.001). This experimental study showed that low-dose adalimumab appears to have a beneficial effect on intestinal injury induced with H/R in neonatal rats.
肿瘤坏死因子-α(TNF-α)在缺氧/复氧(H/R)诱导的肠道损伤中具有重要作用。研究表明,用英夫利昔单抗阻断 TNF-α对实验性坏死性小肠结肠炎和缺氧性肠损伤具有有益作用。然而,尚无关于阿达木单抗对 H/R 诱导的肠道损伤影响的数据。因此,我们旨在确定阿达木单抗在新生大鼠这种损伤中的潜在剂量依赖性作用。Wistar 白化大鼠幼崽被分配到以下四个组之一:对照组、缺氧组、低剂量阿达木单抗(5mg/kg/天)治疗组(LDAT)和高剂量阿达木单抗(50mg/kg/天)治疗组(HDAT)。在实验的第四天,除对照组外,所有大鼠均暴露于 H/R 后安乐死。测量肠组织中的丙二醛(MDA)、髓过氧化物酶(MPO)、TNF-α、总抗氧化能力(TAC)和总氧化能力(TOC)。使用 TAC 和 TOC 值计算氧化应激指数(OSI)。还评估了组织样本中的组织学损伤评分(HIS)。LDAT 和 HDAT 组的 MDA 水平显著低于 H/R 组(p<0.001)。LDAT 组的 TNF-α水平显著低于 H/R 组(p<0.001)。H/R 组的 OSI 显著高于对照组和 LDAT 组(p<0.001)。LDAT 组的平均 HIS 值显著低于 H/R 组和 HDAT 组(p<0.001)。这项实验研究表明,低剂量阿达木单抗似乎对新生大鼠 H/R 诱导的肠道损伤具有有益作用。