Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
Department of Pharmacology, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
Chem Biol Interact. 2016 Oct 25;258:266-75. doi: 10.1016/j.cbi.2016.09.011. Epub 2016 Sep 16.
Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model.
Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats.
Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model.
Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.
先前阻断肾素-血管紧张素系统（RAAS）已被证明可有效预防胃损伤。因此，本研究旨在研究阿利克仑（直接阻断肾素）对消炎痛诱导的胃损伤模型的影响。
在阿尔卑斯白化 Wistar 大鼠的消炎痛诱导的胃损伤模型中评估了阿利克仑的作用。以法莫替丁作为标准抗溃疡药物研究了其作用。对胃组织进行溃疡面积测定的体视学分析、氧化状态测定的生化分析以及组织细胞因子和环氧化酶测定的分子分析。此外，为了阐明阿利克仑的抗溃疡作用机制，还在大鼠中应用了幽门结扎诱导的胃酸分泌模型。
阿利克仑能够抑制消炎痛诱导的溃疡形成。它还抑制了肾素，从而减少了溃疡形成过程中过度产生的血管紧张素 II。阿利克仑改善了胃的氧化状态和细胞因子谱，这很可能是由于血管紧张素 II 浓度增加而受损。阿利克仑还增加了保护性前列腺素 E2 浓度。最后，阿利克仑并未改变幽门结扎模型中的胃酸。
阿利克仑通过抑制 RAAS 及其终产物血管紧张素 II，减少炎症细胞因子和氧化应激，对胃组织发挥保护作用。阿利克仑还显著增加了保护性因素，如 PGE2，但不影响攻击性因素，如胃酸。
