Hypergravity enhances the therapeutic effect of dexamethasone in allergic asthma and rhinitis animal model.
Hypergravity enhances the therapeutic effect of dexamethasone in allergic asthma and rhinitis animal model.
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DOI：
10.1371/journal.pone.0197594
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kim YH
中科院分区：
文献类型：
--
作者：
Jang TY;Jung AY;Kwon S;Kim YH
我们研究了地塞米松对小鼠过敏性哮喘和鼻炎的治疗效果是否在暴露于超重力时增强。将40只小鼠分为5组（n = 8/组）：对照组腹腔内（i. p.）和鼻内（i.n.）;哮喘组给予i. p. I.N.卵白蛋白（OVA）诱导变应性哮喘/鼻炎; Dexa/Hypergravity组在诱导过敏性哮喘/鼻炎模型的同时，同时给予地塞米松（0.75 mg/kg），Dexa/Hypergravity组在诱导过敏性哮喘/鼻炎模型的同时给予5G的超重力，持续30 d。与哮喘组相比，Dexa组和超重组显示血清总IgE水平显著降低（p<0.05）。与Dexa组相比，Dexa/超重组显示出更大的IgE降低（p = 0.040）。与单药治疗组相比，Dexa/超重组在BAL液中显示出显著更少的嗜酸性粒细胞（p<0.05）。Dexa/超重组显示肺和鼻腔中的嗜酸性粒细胞浸润显著减少（p<0.05）。与Dexa组相比，超重组和Dexa/超重组的EC-SOD（细胞外超氧化物歧化酶）表达显著上调（p<0.05）。总之，超重力增强了地塞米松在过敏性哮喘和鼻炎小鼠模型中的治疗效果。因此，联合应用可能是一种很有前途的策略，其机制之一可能是上调EC-SOD的表达。
We investigated whether the therapeutic effects of dexamethasone for allergic asthma and rhinitis were enhanced in mice when exposed to hypergravity. Forty mice were divided into 5 groups (n = 8/group): Control group received saline intraperitoneally (i.p.) and intranasally (i.n.); Asthma group received i.p./i.n. ovalbumin (OVA) for inducing allergic asthma/rhinitis; Dexa group received i.n. dexamethasone (0.75 mg/kg) 30 minutes before each OVA challenge; Hypergravity group was subjected to allergic asthma/rhinitis as well as exposed to 5 G hypergravity for 30 days; Finally in Dexa/Hypergravity group, hypergravity and dexamethasone were used simultaneously during induction of allergic asthma/rhinitis. Dexa group and Hypergravity group showed a significant decrease in serum total IgE levels compared to the Asthma group (p<0.05). Dexa/Hypergravity group showed greater IgE decrease compared with Dexa group (p = 0.040). Compared with the monotherapy groups, Dexa/Hypergravity group showed significantly fewer eosinophils in BAL fluid (p<0.05). Dexa/Hypergravity group showed significantly decreased eosinophilic infiltration into the lungs and nasal cavity (p<0.05). EC-SOD (extracellular superoxide dismutase) expression was significantly upregulated in the Hypergravity group and Dexa/Hypergravity group, compared with the Dexa group (p<0.05). In conclusion, hypergravity enhanced the therapeutic effect of dexamethasone in a murine model of allergic asthma and rhinitis. Therefore, combination could be a promising strategy, and one of its mechanisms could be up-regulation of EC-SOD expression.
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