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内皮素-1 和内皮素受体拮抗剂在变应性鼻炎炎症中的作用:卵清蛋白诱导的大鼠模型。

The role of endothelin-1 and endothelin receptor antagonists in allergic rhinitis inflammation: ovalbumin-induced rat model.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Ataturk University, Medical Faculty, Erzurum, Turkey.

Department of Pharmacology, Ataturk University, Medical Faculty, Erzurum, Turkey.

出版信息

Rhinology. 2016 Sep;54(3):266-72. doi: 10.4193/Rhino15.059.

DOI:10.4193/Rhino15.059
PMID:27016898
Abstract

OBJECTIVE

Desloratadine is a biologically active metabolite of loratadine which is indicated for the treatment of allergic rhinitis. Bosentan is a dual endothelin receptor antagonist used to treatment of pulmonary artery hypertension (PAH). In this study, we aimed to determine the role of endothelins in allergic rhinitis (AR) and the effects of endothelin receptor antagonists in AR rat models through comparison with desloratadine.

METHODS

In total, 20 adult Sprague-Dawley rats were used in this study. An ovalbumin-induced allergic rhinitis model was formed in three study groups except for the control group. Bosentan (100 mg/kg/day) was given to the bosentan-treated group for 7 days and desloratadine (10 mg/kg/day) was administered to the antihistaminic-treated group for 7 days. Nasal symptom scorings and histopathological examinations of the nasal tissues were carried out. Serum IgE levels and ET-1 and TNF-alpha mRNA expression levels were analysed. Between group comparisons for nasal symptoms, histopathological analysis, and molecular analyses were performed with a one-way ANOVA and Duncans multiple comparison tests. Significance was accepted at p smaller than 0.05.

RESULTS

Bosentan inhibited nasal symptom more significantly than desloratadine. The IgE level, ET-1 and TNF-alpha mRNA expression levels statistically increased in the allergic rhinitis group when compared to other groups. Conversely, the bosentan-treatment group showed a significant recovery from the same parameters. The deterioration in histopathological parameters reached the highest levels in the allergic rhinitis group. The histopathological findings were close to those of the control group in the bosentan and antihistaminic-treated group.

CONCLUSIONS

ET-1 is one of the mediators that impact AR development and ET-1 antagonists can be useful for symptom control and for decreasing allergic inflammation in AR patients.

摘要

目的

地氯雷他定是氯雷他定的生物活性代谢物,用于治疗过敏性鼻炎。波生坦是一种双重内皮素受体拮抗剂,用于治疗肺动脉高压(PAH)。在这项研究中,我们旨在通过与地氯雷他定比较,确定内皮素在过敏性鼻炎(AR)中的作用以及内皮素受体拮抗剂在 AR 大鼠模型中的作用。

方法

总共使用了 20 只成年 Sprague-Dawley 大鼠。除对照组外,在三个研究组中形成卵清蛋白诱导的过敏性鼻炎模型。给予波生坦治疗组 100mg/kg/天,地氯雷他定治疗组 10mg/kg/天,连续 7 天。进行鼻症状评分和鼻组织的组织病理学检查。分析血清 IgE 水平以及 ET-1 和 TNF-α mRNA 表达水平。采用单因素方差分析和 Duncan 多重比较检验对组间比较进行鼻症状、组织病理学分析和分子分析。p 值小于 0.05 被认为具有统计学意义。

结果

波生坦比地氯雷他定更能抑制鼻症状。与其他组相比,过敏性鼻炎组的 IgE 水平、ET-1 和 TNF-α mRNA 表达水平显著升高。相反,波生坦治疗组在相同参数上表现出显著的恢复。组织病理学参数的恶化在过敏性鼻炎组中达到最高水平。在波生坦和抗组胺治疗组中,组织病理学发现与对照组接近。

结论

ET-1 是影响 AR 发展的介质之一,ET-1 拮抗剂可用于控制症状并减少 AR 患者的过敏炎症。

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