Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma
Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma
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白藜芦醇抑制哮喘小鼠模型中粘液过量产生和 MUC5AC 表达
DOI：
10.3892/mmr.2015.4520
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发表时间：
2016-01-01
影响因子：
3.4
通讯作者：
Wang, Xiong-Biao
中科院分区：
文献类型：
--
作者：
Ni, Zhen-Hua;Tang, Ji-Hong;Wang, Xiong-Biao
先前的体外研究表明，白藜芦醇能够显著抑制黏液主要成分MUC5AC的上调；这表明白藜芦醇可能具有调节粘液过量产生的潜力。然而，关于白藜芦醇介导的MUC5AC体内过度生成的预防研究较少，白藜芦醇调节MUC5AC表达的机制尚未阐明。在本研究中，使用卵清蛋白（OVA）挑战的哮喘小鼠模型来评估白藜芦醇治疗对体内粘液产生的影响。结果表明，白藜芦醇显著抑制ova诱导的气道炎症和粘液生成。此外，ova激发小鼠MUC5AC mRNA和蛋白表达水平升高，而白藜芦醇显著抑制了这一作用。小鼠钙活化氯通道（mCLCA）3的表达水平在白藜芦醇处理后也降低了，mCLCA 3是MUC5AC产生的重要关键介质。此外，体外研究表明，白藜芦醇以剂量依赖性的方式显著抑制人(h)CLCA1和MUC5AC的表达。这些结果表明，白藜芦醇在体内可有效防止粘液过量产生和MUC5AC的表达，其潜在机制可能与调节mCLCA3/hCLCA1信号通路有关。
Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin SAC (MUC5AC), a major component of mucus; thus indicating that resveratrol may have potential in regulating mucus overproduction. However, there have been few studies regarding the resveratrol-mediated prevention of MUC5AC overproduction in vivo, and the mechanisms by which resveratrol regulates MUC5AC expression have yet to be elucidated. In the present study, an ovalbumin (OVA)-challenged murine model of asthma was used to assess the effects of resveratrol treatment on mucus production in vivo. The results demonstrated that resveratrol significantly inhibited OVA-induced airway inflammation and mucus production. In addition, the mRNA and protein expression levels of MUC5AC were increased in the OVA-challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium-activated chloride channel (mCLCA)3, an important key mediator of MUC5AC production, were also reduced following resveratrol treatment. Furthermore, in vitro studies demonstrated that resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose-dependent manner. These results indicated that resveratrol was effective in preventing mucus overproduction and MUC5AC expression in vivo, and its underlying mechanism may be associated with regulation of the mCLCA3/hCLCA1 signaling pathway.