Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
Environ Toxicol Pharmacol. 2022 Apr;91:103833. doi: 10.1016/j.etap.2022.103833. Epub 2022 Feb 24.
Ulcerative colitis (UC) is a chronic colon inflammation that is linked to exposure to environmental factors leading to improper immune responses to enteric microbes in genetically susceptible individuals. This study was designed to explore the possible protective impact of Empagliflozin (EMPA), an anti-diabetic sodium-glucose cotransporter-2 (SGLT2) inhibitor, on acetic acid (AA)-induced UC in rats.
Intrarectal instillation of AA (2 ml, 3% v/v) was used to induce UC. EMPA (10 & 30 mg/kg) was administered orally for 11 days.
EMPA successfully counteracted AA-induced UC that was manifested by improving colonic histopathological architecture concomitant with a marked decrease in disease activity index (DAI), colon weight, weight/length ratio, serum lactate dehydrogenase (LDH) activity, and C-reactive protein (CRP) level. Additionally, EMPA successfully restored the disrupted oxidant/antioxidants balance induced by AA. Moreover, EMPA significantly induced silent information regulator-1(SIRT-1) expression along with a significant reduction in phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT), nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF)-α and interleukins (IL-1β and IL-6) expression in colonic tissues. Furthermore, EMPA successfully improved the colonic barrier that was appeared from the marked induction of tight junction proteins level (occludin and claudin-1).
EMPA successfully counteracted AA-induced UC in rats via the modulation of SIRT1/PI3K/AKT/NF-κB inflammatory pathway, normalizing oxidant/antioxidants balance, and improving the integrity of colon barrier.
溃疡性结肠炎（UC）是一种慢性结肠炎症，与暴露于环境因素有关，这些因素导致遗传易感个体对肠道微生物产生不当的免疫反应。本研究旨在探讨抗糖尿病钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂恩格列净（EMPA）对乙酸（AA）诱导的大鼠 UC 的可能保护作用。
采用直肠内滴注 AA（2ml，3%v/v）诱导 UC。EMPA（10 和 30mg/kg）口服给药 11 天。
EMPA 成功地对抗了 AA 诱导的 UC，表现为改善结肠组织病理学结构，同时显著降低疾病活动指数（DAI）、结肠重量、重量/长度比、血清乳酸脱氢酶（LDH）活性和 C 反应蛋白（CRP）水平。此外，EMPA 成功地恢复了 AA 诱导的氧化应激/抗氧化剂平衡的破坏。此外，EMPA 显著诱导沉默信息调节因子-1（SIRT-1）的表达，同时显著降低磷酸肌醇-3-激酶（PI3K）、蛋白激酶 B（AKT）、核因子 kappa B（NF-κB）、肿瘤坏死因子（TNF）-α 和白细胞介素（IL-1β 和 IL-6）在结肠组织中的表达。此外，EMPA 成功地改善了结肠屏障，表现在紧密连接蛋白水平（occludin 和 claudin-1）的显著诱导。
EMPA 通过调节 SIRT1/PI3K/AKT/NF-κB 炎症途径、调节氧化应激/抗氧化剂平衡和改善结肠屏障的完整性，成功地对抗了 AA 诱导的大鼠 UC。
