Effects of 4-DAMP on allergic rhinitis in guinea pigs and its potential mechanism

作者全名："Huang, Yu; Long, Rui; Tang, Yiding; Li, Juan; Meng, Long; Yang, Jiadan; Qiu, Feng"

作者地址："[Huang, Yu; Long, Rui; Tang, Yiding; Li, Juan; Meng, Long; Yang, Jiadan; Qiu, Feng] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Qiu, F (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：ANNALS OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000828405900001

JCR分区：Q3

影响因子：3.616

年份：2022

卷号：10

期号：14

开始页：　

结束页：　

文献类型：Article

关键词："1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP); allergic rhinitis (AR); M3 receptor; hypersecretion; chronic inflammatory"

摘要："Background: Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mainly mediated by immunoglobulin E (IgE), which seriously affects the life quality of affected patients. This study aimed to observe the effects of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; a selective M3 receptor antagonist) on ovalbumin (OVA)-induced AR guinea pigs, and to explore its potential mechanism of involvement. Methods: An AR model was established by inducing male guinea pigs (4-6 weeks of age) with OVA. AR guinea pigs were randomly divided into a model group, 0.6 mg/kg ipratropium bromide (IB) group, 0.12 and 0.6 mg/kg 4-DAMP group (n=18). The 0.6 mg/kg IB group, 0.12 and 0.6 mg/kg 4-DAMP group animals were treated with IB (0.6 mg/kg) and 4-DAMP (0.12 or 0.6 mg/kg) by intranasal instillation per nostril daily. Animals in the model group and normal group were treated with saline as control. The AR symptom scores were counted and nasal secretion weights were measured. Histopathological methods were used to observe nasal mucosa. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of histamine and cytokines. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expressions of mucin 5AC (MUC5AC), matrix metalloproteinase 9 (MMP9), and epidermal growth factor receptor (EGFR). Results: Compared with model group animals, the AR symptom scores and nasal secretion weights of animals treated with 4-DAMP were reduced significantly, goblet cell metaplasia was reversed, and eosinophil infiltration was visibly alleviated. The levels of histamine and cytokines in nasal lavage fluid (NLF) were decreased, and the protein and messenger RNA (mRNA) expressions of MUC5AC, MMP9, and EGFR were inhibited. Conclusions: Treatment with 4-DAMP has a certain effect on AR, especially for mucus hypersecretion, which provides a new idea for clinical treatment of AR."

基金机构：National Natural Science Foundation of China [81700895]; Basic Science and Frontier Technology Research Project of Chongqing [cstc2017jcyjAX0223]

基金资助正文：This work was supported by the National Natural Science Foundation of China (No. 81700895) and Basic Science and Frontier Technology Research Project of Chongqing (No. cstc2017jcyjAX0223).