Tarani Shaghayegh, Vahabzadeh Gelareh, Fallah Huseini Hasan, Khavandegar Armin, Tavakoli-Far Bahareh, Jazayeri Roshanak
Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Med J Islam Repub Iran. 2024 Sep 2;38:100. doi: 10.47176/mjiri.38.100. eCollection 2024.
The role of histamine H3 receptors (H3Rs) in gastric protection and anti-inflammatory function is controversial. In this study, we investigated the gastroprotective effect of a histamine H3 receptor antagonist drug, betahistine, on cytokine-induced neutrophil chemoattractant (CINC) gene expression in a rat model of indomethacin-induced gastric mucosal injury.
In this experiment, rats were divided into four groups; the control group received no treatment, group 2 was treated with indomethacin at a dose of 25 mg/kg, group 3 pre-treated with famotidine at a dose of 50 mg/kg, and group 4 pre-treated with betahistine (as a reference drug) at a dose of 50 mg/kg. The last two groups were followed by indomethacin administration (25 mg/kg), three days later. The obtained values were expressed as the mean and standard error of the mean (mean ± SEM). The level of statistical significance was set at α = 0.05.
Indomethacin treatment resulted in large ulcerative lesions with a mean ulcer index of 29± 13.63 mm. However, ulcerative indices were significantly improved in groups pre-treated with famotidine (15.5 ± 8.68 mm; < 0.05) and betahistine (11±5.66 mm, < 0.01), compared to the indomethacin-treated group. The expression levels of gastric CINC-2ɑ were significantly elevated in indomethacin-induced groups by 0.028±0.05 in the indomethacin group, 0.005±0.01 in indomethacin + famotidine, and 0.012±0.03 in indomethacin + betahistine groups, compared to the control group ( < 0.05). Besides, pre-treatment with betahistine significantly reduced the expression of CINC-2ɑ induced by indomethacin administration ( < 0.05).
Betahistine for five days before administrating indomethacin reduced the ulcer index and downregulated the expression of CINC-2α significantly. Overall, pre-treatment with betahistine protects against the gastric damage induced by indomethacin by lowering the expression of CINC-2ɑ.
组胺H3受体（H3Rs）在胃保护和抗炎功能中的作用存在争议。在本研究中，我们在吲哚美辛诱导的胃黏膜损伤大鼠模型中，研究了组胺H3受体拮抗剂药物倍他司汀对细胞因子诱导的中性粒细胞趋化因子（CINC）基因表达的胃保护作用。
在本实验中，大鼠被分为四组；对照组未接受任何治疗，第2组用25mg/kg剂量的吲哚美辛治疗，第3组用50mg/kg剂量的法莫替丁预处理，第4组用50mg/kg剂量的倍他司汀（作为参考药物）预处理。后两组在三天后给予吲哚美辛（25mg/kg）。所得值表示为平均值和平均标准误差（平均值±标准误）。统计学显著性水平设定为α = 0.05。
吲哚美辛治疗导致大面积溃疡性病变，平均溃疡指数为29±13.63mm。然而，与吲哚美辛治疗组相比，用 法莫替丁（15.5±8.68mm；P<0.05）和倍他司汀（11±5.66mm，P<0.01）预处理的组溃疡指数显著改善。与对照组相比，吲哚美辛诱导组胃CINC-2ɑ的表达水平显著升高，吲哚美辛组为0.028±0.05，吲哚美辛+法莫替丁组为0.005±0.01，吲哚美辛+倍他司汀组为0.012±0.03（P<0.05）。此外，倍他司汀预处理显著降低了吲哚美辛给药诱导的CINC-2ɑ表达（P<0.05）。
在给予吲哚美辛前五天使用倍他司汀可降低溃疡指数，并显著下调CINC-2α的表达。总体而言，倍他司汀预处理通过降低CINC-2ɑ的表达来保护免受吲哚美辛诱导的胃损伤。
