Khotib Junaidi, Rahmadi Mahardian, Ardianto Chrismawan, Nisak Khoirotin, Oktavia Rianur, Ratnasari Ayu, Dinintia Yunita, Shinta Dewi Wara, Aryani Toetik
Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60286, Indonesia, Phone: +62 82233209135, Office: +62 31 5033710, Fax: +62 31 5020514.
J Basic Clin Physiol Pharmacol. 2019 Feb 7;30(2):195-203. doi: 10.1515/jbcpp-2018-0067.
Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.
背景 选择性5-羟色胺再摄取抑制剂（SSRIs）最近已成为溃疡和胃出血新治疗方法的潜在候选药物。热休克蛋白70（Hsp70）在细胞对非甾体抗炎药（NSAIDs）的抵抗中起重要作用。然而，缺乏证据表明氟伏沙明募集Hsp70以影响应激性胃溃疡。因此，我们研究了氟伏沙明对NSAID诱导和应激性胃溃疡的影响以及Hsp70可能的参与情况。方法 在该研究中使用ICR小鼠。通过水浸加束缚法进行应激诱导。通过口服吲哚美辛产生NSAID诱导的胃溃疡。在应激诱导和吲哚美辛治疗前30分钟口服给予氟伏沙明。结果 应激和吲哚美辛治疗显著增加溃疡指数和腔内出血评分。应激和吲哚美辛治疗也显著增加Hsp70的表达。氟伏沙明在两种溃疡模型中均显著降低溃疡指数和腔内出血。此外，氟伏沙明进一步增加了应激和吲哚美辛治疗小鼠胃组织中Hsp70的表达。结论 我们的结果表明氟伏沙明可能对应激性和NSAID诱导的胃溃疡具有保护作用。此外，本研究提示Hsp70可能参与氟伏沙明对胃溃疡的改善作用。
