Abstract

Indomethacin is a widely used nonsteroidal anti-inflammatory drug; however, its clinical utility is accompanied by serious adverse reactions including peptic ulcers. The current study aims to investigate the protective potential of perindopril against indomethacin-induced gastric injury in rats. Perindopril (4 mg/kg) was administered orally for 7 days and indomethacin (60 mg/kg, single oral dose) was administered on the 7^th day, 1 h after perindopril administration. Pantoprazole was used as a standard agent. Ulcer index (UI), preventive index ratio (PI), histopathological examination, oxidative stress, and inflammatory biomarkers were investigated. Perindopril significantly decreased UI while increased PI and counteracted histopathological aberrations induced by indomethacin. It alleviated indomethacin-induced oxidative stress by lowering NO while increasing GSH content and superoxide dismutase activity. Perindopril significantly downregulated TNF-α and asymmetric dimethylarginine (ADMA), while significantly upregulated COX-2, PGE-2, dimethylarginine dimethylaminohydrolase-1 (DDAH-1), ANG-(1-7), and ACE-2 expression. Together, these findings suggest the gastroprotective effects of perindopril through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling.

• HIGHLIGHTS

• Perindopril attenuated gastric histopathological damage.

• It increased GSH content and SOD activity while decreased NO content.

• It modulated gastric ADMA and DDAH-1 activity.

• It reduced TNF-α, while increased COX-2 and PGE-2 expression.

• It upregulated ACE-2 activity and ANG-(1-7) protein expression.

摘要

消炎痛是一种广泛使用的非甾体抗炎药；然而，它的临床应用伴随着严重的不良反应，包括消化性溃疡。本研究旨在探讨培哚普利对吲哚美辛诱导的大鼠胃损伤的保护作用。^{培哚普利（4 mg/kg）口服给药7天，消炎痛（60 mg/kg，单次}口服）于第7天给药天，培哚普利给药后 1 小时。泮托拉唑用作标准剂。研究了溃疡指数（UI）、预防指数比（PI）、组织病理学检查、氧化应激和炎症生物标志物。培哚普利显着降低 UI，同时增加 PI 并抵消消炎痛诱导的组织病理学异常。它通过降低 NO 同时增加 GSH 含量和超氧化物歧化酶活性来缓解吲哚美辛诱导的氧化应激。Perindopril 显着下调 TNF-α 和不对称二甲基精氨酸 (ADMA)，同时显着上调 COX-2、PGE-2、二甲基精氨酸二甲基氨基水解酶-1 (DDAH-1)、ANG-(1-7) 和 ACE-2 的表达。总之，这些发现表明培哚普利通过调节 DDAH-1/ADMA 和 ACE-2/ANG-(1-7) 信号传导具有胃保护作用。

• 强调

• 培哚普利减轻胃组织病理学损伤。

• 它增加了GSH含量和SOD活性，同时降低了NO含量。

• 它调节胃 ADMA 和 DDAH-1 活性。

• 它降低了 TNF-α，同时增加了 COX-2 和 PGE-2 的表达。

• 它上调 ACE-2 活性和 ANG-(1-7) 蛋白表达。