Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt; Department of Medical Physiology, Faculty of Medicine, Al-Baha University, Saudi Arabia.
Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia; Department of Histology and Cell Biology of Medicine, Benha University, Egypt.
Life Sci. 2021 May 15;273:119297. doi: 10.1016/j.lfs.2021.119297. Epub 2021 Mar 6.
Stress-induced gastritis is a common problem in the intensive care unit. Zeaxanthin (ZE), a non-provitamin A carotenoid has been known to exert antioxidant and anti-inflammatory effects. In this study, we examined the effect of ZE on water avoidance stress (WAS)-induced gastritis in rats. 24 Sprague' Dawley male rats were divided into four groups; control, ZE, WAS and WAS+ZE. In the stressed rats, treatment with ZE effectively downregulated the gastric levels of total oxidant status (TOS), myeloperoxidase (MPO) and malondialdehyde (MDA), with significant upregulation of the antioxidant enzymes' activities and gastric levels of prostagladin-E2 (PGE2) as compared to the untreated stressed one. As noticed in the present study, ZE significantly decrease the gastric levels of interleukin-1 β (IL-1β) and IL-6 as well as suppression of nuclear transcription factor kappa-B (NF-κB) immunohistochemical expression together with upregulation of trefoil factor-1 (TFF-1) gene expression. Moreover, in the untreated WAS-induced gastritis group, gastrin and corticosterone levels were significantly increased together with upregulation of the gene expression of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), PI3K, Akt and JNK in the gastric tissues, which significantly improved by ZE administration. These all positive effects of ZE reflected on reduction of microscopic gastric mucosal damage and inflammatory cell infiltration with improvement of ulcer score. Our results discover that ZE has a new gastroprotective effect against stress-induced gastritis in rats, primarily through its antioxidative and anti-inflammatory effects, which are expressed in the regulation of the MMP-9 and HIF-1α signaling pathways.
应激性胃炎是重症监护病房的常见问题。叶黄素（ZE）作为一种非维生素 A 类胡萝卜素，具有抗氧化和抗炎作用。在这项研究中，我们研究了 ZE 对水回避应激（WAS）诱导的大鼠胃炎的影响。将 24 只雄性 Sprague' Dawley 大鼠随机分为 4 组：对照组、ZE 组、WAS 组和 WAS+ZE 组。在应激大鼠中，与未治疗的应激大鼠相比，ZE 处理可有效下调胃总氧化状态（TOS）、髓过氧化物酶（MPO）和丙二醛（MDA）水平，显著上调抗氧化酶活性和胃内前列腺素 E2（PGE2）水平。如本研究中所注意到的，ZE 可显著降低胃内白细胞介素-1β（IL-1β）和 IL-6 水平，并抑制核转录因子 kappa-B（NF-κB）免疫组化表达，同时上调三叶因子-1（TFF-1）基因表达。此外，在未治疗的 WAS 诱导的胃炎组中，胃泌素和皮质酮水平显著升高，同时缺氧诱导因子-1α（HIF-1α）、基质金属蛋白酶-9（MMP-9）、PI3K、Akt 和 JNK 的基因表达上调，这些变化在 ZE 给药后得到显著改善。ZE 的这些积极作用反映在胃黏膜损伤和炎症细胞浸润的减少以及溃疡评分的改善上。我们的结果表明，ZE 对大鼠应激性胃炎具有新的胃保护作用，主要通过其抗氧化和抗炎作用，通过调节 MMP-9 和 HIF-1α信号通路来实现。
