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瑞舒伐他汀再利用预防大鼠乙醇诱导急性胃溃疡:生化、组织学和超微结构观点。

Rosuvastatin repurposing for prophylaxis against ethanol-induced acute gastric ulceration in rats: a biochemical, histological, and ultrastructural perspective.

机构信息

Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha, 13518, Egypt.

Anatomy Department, College of Medicine, Umm Al-Qura University, 24230, Makkah, Saudi Arabia.

出版信息

Inflammopharmacology. 2024 Oct;32(5):3475-3498. doi: 10.1007/s10787-024-01513-z. Epub 2024 Jul 24.

Abstract

Ethanol (EtOH) consumption is frequently associated with acute and chronic gastrointestinal disorders. Rosuvastatin (RSV), a third-generation statin, has demonstrated certain biological functions beyond its lipid-lowering properties. This study is designed to explore the gastroprotective impact of RSV in a rat model of EtOH-induced gastric ulceration in a dose-dependent manner through the evaluation of oxidant/antioxidant biomarkers, inflammatory myeloperoxidase (MPO) enzyme activity, and prostaglandin E2 (PGE) levels in gastric tissues, along with histopathological examination of the gastric tissues. Therefore, 40 adult male rats were randomly divided into five equal groups as control, EtOH (gastric ulcer), RSV-low dose plus EtOH and RSV-high dose plus EtOH. The EtOH rat model of gastric ulceration was achieved by intragastric administration of a single dose of EtOH. Seven days before EtOH administration, rats were orally administered either omeprazole (20 mg/kg/day) or RSV (10 mg/kg/day or 20 mg/kg/day). RSV administration enhanced the antioxidant glutathione reduced, countered oxidative malondialdehyde, augmented cytoprotective PGE, suppressed inflammatory MPO enzyme activity in gastric tissues, decreased ulcer index scoring, increased the percentage of ulcer inhibition, and reversed the associated histological and ultrastructural abnormalities, additionally, RSV treatment resulted in weak positive nuclear staining for the inflammatory nuclear factor kappa B in a dose-dependent manner. It is concluded that RSV demonstrates gastroprotective potential, attributable at least in part, to its antioxidant and anti-inflammatory properties, as well as its ability to promote ulcer protection through the maintenance of mucosal content and PGE levels. Thus, RSV therapy emerges as a safe option for patients with gastric ulcers.

摘要

乙醇(EtOH)的摄入常与急性和慢性胃肠道疾病有关。瑞舒伐他汀(RSV),一种第三代他汀类药物,除了降脂作用外,还具有某些生物学功能。本研究旨在通过评估氧化应激/抗氧化生物标志物、炎症髓过氧化物酶(MPO)酶活性和胃组织中环前列腺素 E2(PGE)水平,以及胃组织的组织病理学检查,以剂量依赖的方式,在乙醇诱导的大鼠胃溃疡模型中探究 RSV 的胃保护作用。因此,将 40 只成年雄性大鼠随机分为 5 个相等的组:对照组、乙醇(胃溃疡)组、低剂量 RSV 加乙醇组和高剂量 RSV 加乙醇组。通过单次胃内给予乙醇来建立乙醇诱导的大鼠胃溃疡模型。在给予乙醇前 7 天,大鼠经口给予奥美拉唑(20mg/kg/天)或 RSV(10mg/kg/天或 20mg/kg/天)。RSV 给药可增强抗氧化谷胱甘肽还原,拮抗氧化丙二醛,增加细胞保护 PGE,抑制胃组织中的炎症 MPO 酶活性,降低溃疡指数评分,增加溃疡抑制百分比,并逆转相关的组织学和超微结构异常,此外,RSV 治疗以剂量依赖的方式导致炎症核因子 kappa B 的核弱阳性染色。综上所述,RSV 具有胃保护作用,这至少部分归因于其抗氧化和抗炎特性,以及通过维持黏膜含量和 PGE 水平促进溃疡保护的能力。因此,RSV 治疗成为胃溃疡患者的安全选择。

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