Department of Forensic Toxicology, Judicial Identification Center of Shaoxing University, Shaoxing 312000, China.
Department of Pharmacolgoy, Medical College of Shaoxing University, Shaoxing 312000, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Mar 1;50(3):246-253. doi: 10.1093/abbs/gmy002.
Gastric ulcers (GUs) are common pathologies that affect many people around the world. Excessive alcohol consumption is one of the main causes of GUs; however, there are still lack of effective drugs for the prevention or therapy of GUs. In this study, we evaluated the protective effects and possible mechanisms of kaempferol (KAE) against acute ethanol-induced lesions to the gastric mucosa in mice. Fasted mice were orally given vehicle (0.9% saline), omeprazole (20 mg/kg), or KAE (40, 80, or 160 mg/kg) for 1 h in different experimental sets prior to the establishment of the GU model by challenge with absolute ethanol (10 ml/kg). Animals were euthanized 1 h after ethanol intake, and their plasma and stomach tissues were subject to further examination. Macroscopic and microscopic lesions, and immunological and biochemical parameters were observed. The effects of inflammation were investigated using the following indicators: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, myeloperoxidase (MPO), and nitric oxide (NO). Results showed that KAE significantly decreased the ulcer index, increased the preventive index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. KAE decreased MPO activity and pro-inflammatory cytokine (TNF-α, and IL-1β) levels, and improved NO levels. The gastroprotective activity of KAE might be attributed to the preservation of gastric mucous glycoproteins levels, thus by inhibiting neutrophil accumulation and MPO activity, adjusting the levels of pro-inflammatory cytokines, and improving NO production.
胃溃疡（GU）是一种常见的疾病，影响着全世界许多人。过量饮酒是 GU 的主要原因之一；然而，目前仍然缺乏预防或治疗 GU 的有效药物。在本研究中，我们评估了山柰酚（KAE）对小鼠急性乙醇诱导的胃黏膜损伤的保护作用及其可能的机制。在不同的实验中，禁食的小鼠在建立 GU 模型前 1 h 经口给予载体（0.9%生理盐水）、奥美拉唑（20 mg/kg）或 KAE（40、80 或 160 mg/kg），1 h 后用无水乙醇（10 ml/kg）进行挑战。乙醇摄入后 1 h 处死动物，对其血浆和胃组织进行进一步检查。观察宏观和微观病变以及免疫和生化参数。使用以下指标研究炎症的影响：肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、IL-6、髓过氧化物酶（MPO）和一氧化氮（NO）。结果表明，KAE 能显著降低溃疡指数，增加预防指数，完全保护黏膜免受损伤，并保留胃黏膜糖蛋白。KAE 降低了 MPO 活性和促炎细胞因子（TNF-α和 IL-1β）水平，并提高了 NO 水平。KAE 的胃保护活性可能归因于胃黏膜糖蛋白水平的保持，从而通过抑制中性粒细胞聚集和 MPO 活性，调节促炎细胞因子水平，以及改善 NO 的产生。
