Ni Zhen-Hua, Tang Ji-Hong, Chen Guo, Lai Yi-Min, Chen Qing-Ge, Li Zao, Yang Wei, Luo Xu-Min, Wang Xiong-Biao
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Mol Med Rep. 2016 Jan;13(1):287-94. doi: 10.3892/mmr.2015.4520. Epub 2015 Nov 6.
Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin 5AC (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.
先前的体外研究表明，白藜芦醇能够显著抑制粘蛋白5AC（MUC5AC，黏液的主要成分）的上调；因此表明白藜芦醇可能具有调节黏液过度产生的潜力。然而，关于白藜芦醇在体内介导预防MUC5AC过度产生的研究较少，且白藜芦醇调节MUC5AC表达的机制尚未阐明。在本研究中，使用卵清蛋白（OVA）激发的哮喘小鼠模型来评估白藜芦醇治疗对体内黏液产生的影响。结果表明，白藜芦醇显著抑制OVA诱导的气道炎症和黏液产生。此外，OVA激发的小鼠中MUC5AC的mRNA和蛋白表达水平升高，而白藜芦醇治疗显著抑制了这种作用。白藜芦醇治疗后，MUC5AC产生的重要关键介质小鼠钙激活氯离子通道（mCLCA）3的表达水平也降低。此外，体外研究表明，白藜芦醇以剂量依赖性方式显著抑制人（h）CLCA1和MUC5AC的表达。这些结果表明，白藜芦醇在体内有效预防黏液过度产生和MUC5AC表达，其潜在机制可能与调节mCLCA3/hCLCA1信号通路有关。
