Deguchi Saori, Iwakami Ayusa, Tujigiwa Mizuki, Otake Hiroko, Mano Yu, Yamamoto Naoki, Nakazawa Yosuke, Misra Manju, Nagai Noriaki
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka,Osaka, 577-8502, Japan.
Department of Pharmacy, Bell Land General Hospital, 500-3, Higashiyama, Naka-ku, Sakai, Osaka, 599-8247, Japan.
J Pharm Health Care Sci. 2023 Nov 28;9(1):44. doi: 10.1186/s40780-023-00312-y.
Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).
Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.
On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.
These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.
非甾体抗炎药（NSAIDs）所致胃肠道损伤是类风湿关节炎（RA）患者的一种严重副作用。然而，有效的治疗策略尚未确立。在本研究中，我们研究了胃黏膜保护药物替普瑞酮（TEP）对类风湿关节炎大鼠（佐剂性关节炎大鼠，AA大鼠）非甾体抗炎药诱导的胃肠道损伤的治疗作用。
通过口服典型的非甾体抗炎药吲哚美辛（IMC）诱导胃肠道损伤。在IMC诱导胃肠道出血后口服TEP，然后切除胃、空肠和回肠。
在给予IMC的第14天，AA大鼠胃、空肠和回肠的损伤面积显著大于正常大鼠。当给AA大鼠口服TEP时，与对照大鼠（IMC诱导的AA大鼠）相比，胃、空肠和回肠的损伤面积显著减小。因此，我们检测了NO合酶2（NOS2）mRNA和一氧化氮（NO）水平，结果显示用TEP治疗后，IMC诱导的AA大鼠中这些指标显著降低。
这些结果表明，口服TEP可能对治疗RA患者非甾体抗炎药诱导的胃肠道损伤有用。
