Pharmacology and Toxicology Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy Ain Shams University, Cairo, Egypt.
Eur J Pharmacol. 2021 Feb 5;892:173812. doi: 10.1016/j.ejphar.2020.173812. Epub 2020 Dec 17.
Gastric ulcer is a very common disease that represent an economic burden. Non-steroidal anti-inflammatory drugs induce ulcer in old patients and in patients with comorbidities. Indomethacin is widely used to induce gastric ulcer in animal models. Diabetic patients are highly susceptible to develop gastric ulcer. Metformin, the first line medication for the treatment of type II diabetes melilites that have many off label uses in non-diabetic patients, has been recently reported to have anti-inflammatory activities. Therefore, this research was conducted to assess the possible healing effects of metformin on gastric ulcers induced by indomethacin in rats. Indomethacin (48 mg/kg) single dose increased stomach acidity, ulcer index and induced histopathological changes. Indomethacin also decreased mucin levels and increased the activity of tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Rho-associated protein kinas-1 (ROCK-1) and decreased the levels of the protective nitric oxide (NO). After the induction of ulcer, rats were treated by omeprazole (30 mg/kg) or metformin (50, 100 or 200 mg/kg). Omeprazole and metformin were found to decrease stomach acidity and ulcer index, restored the histological features and increased mucin levels. Both also decreased the levels of NF-κB, TNF-α, ROCK-1 and increased NO. Metformin exerted ulcer healing effects comparable to that of omeprazole. This can be attributed, at least partly, to its anti-inflammatory activity and increasing NO levels.
胃溃疡是一种非常常见的疾病，给经济带来了负担。非甾体抗炎药会在老年患者和合并症患者中引发溃疡。吲哚美辛被广泛用于诱导动物模型中的胃溃疡。糖尿病患者极易发生胃溃疡。二甲双胍是治疗 II 型糖尿病的一线药物，它在非糖尿病患者中有许多非适应证的用途，最近有报道称其具有抗炎作用。因此，本研究旨在评估二甲双胍对吲哚美辛诱导的大鼠胃溃疡的可能愈合作用。吲哚美辛（48mg/kg）单次剂量增加胃酸、溃疡指数并诱导组织病理学变化。吲哚美辛还降低了粘蛋白水平，增加了肿瘤坏死因子-α（TNF-α）、核因子κB（NF-κB）、Rho 相关蛋白激酶-1（ROCK-1）的活性，并降低了保护性一氧化氮（NO）的水平。在溃疡诱导后，大鼠用奥美拉唑（30mg/kg）或二甲双胍（50、100 或 200mg/kg）治疗。奥美拉唑和二甲双胍均能降低胃酸和溃疡指数，恢复组织学特征并增加粘蛋白水平。两者还降低了 NF-κB、TNF-α、ROCK-1 的水平并增加了 NO。二甲双胍发挥的溃疡愈合作用可与奥美拉唑相媲美。这至少部分归因于其抗炎活性和增加的 NO 水平。
