Antiasthmatic Effects of Resveratrol in Ovalbumin-Induced Asthma Model Mice Involved in the Upregulation of PTEN
Antiasthmatic Effects of Resveratrol in Ovalbumin-Induced Asthma Model Mice Involved in the Upregulation of PTEN
复制标题
白藜芦醇对卵白蛋白诱导的哮喘模型小鼠的抗哮喘作用与 PTEN 上调有关。
DOI：
10.1248/bpb.b14-00610
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发表时间：
2015-04-01
影响因子：
2
通讯作者：
Wang, Xiongbiao
中科院分区：
文献类型：
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作者：
Chen, Guo;Tang, JiHong;Wang, Xiongbiao
白藜芦醇是一种天然多酚化合物，以其抗氧化和抗炎作用而闻名，它具有平喘作用，尽管这些作用的机制仍不清楚。10号染色体上缺失的磷酸酶和紧张素同源基因(PTEN)参与了哮喘的发病过程，哮喘小鼠过表达PTEN可改善哮喘症状。为了探讨白藜芦醇的平喘机制是否与上调PTEN的表达有关，采用卵蛋白(OVA)诱导的小鼠哮喘模型，观察白藜芦醇的治疗作用。用实时定量聚合酶链式反应和免疫组织化学方法检测PTEN基因和蛋白的表达。为了确定是否发生了气道重塑，使用图像分析系统分别测定了气道内壁、粘液层和平滑肌区。以肺上皮细胞系16HBE为研究对象，研究白藜芦醇对肺上皮细胞PTEN表达的调节作用。我们的数据表明，白藜芦醇抑制了OVA诱导的哮喘小鼠的气道炎症和气道重塑。在小鼠哮喘模型中，PTEN的表达减少，尽管白藜芦醇治疗后PTEN的表达恢复。相关效率分析显示，PTEN的表达与气道重塑程度有关。进一步的体外研究表明，SIRT1抑制剂和RNA干扰抑制Sirtuin1(SIRT1)活性降低PTEN蛋白表达，而白藜芦醇减弱SIRT1抑制剂引起的PTEN蛋白表达下降。这些数据提示白藜芦醇在OVA诱导的小鼠哮喘模型中的平喘作用机制，该模型通过激活SIRT1而导致PTEN的上调。
Resveratrol, a natural polyphenolic compound known for its antioxidative and antiinflammatory effects, exerts antiasthmatic effects, although the mechanism underlying these effects remains elusive. The phosphatase and tensin homology deleted on chromosome ten gene (PTEN) is involved in the pathogenesis of asthma, and PTEN overexpression in asthmatic mice improved asthma symptoms. To investigate whether the antiasthmatic mechanisms of resveratrol correlated with the upregulation of PTEN expression, an ovalbumin (OVA)-induced murine asthma model was used to determine the effectiveness of resveratrol treatment. PTEN mRNA and protein expression was assessed with real-time polymerase chain reaction (PCR) and immunochemistry. To determine whether airway remodeling occurred, the inner airway wall, mucous layer, and smooth muscle areas were each determined using an image analysis system. The lung epithelial cell line 16HBE was used to study the regulation of PTEN expression levels by resveratrol in vitro. Our data demonstrated that resveratrol inhibited OVA-induced airway inflammation and airway remodeling in asthmatic mice. PTEN expression was decreased in the murine asthma model, although the expression of PTEN was restored following treatment with resveratrol. Correlation efficiency analysis showed that PTEN expression was associated with the degree of airway remodeling. Further in vitro studies demonstrated that the inhibition of Sirtuin 1 (SIRT1) activity by a SIRT1 inhibitor and RNA interference decreased PTEN protein expression, while resveratrol attenuated the decreases in PTEN expression induced by the SIRT1 inhibitor. These data suggest the mechanism of the antiasthmatic effects of resveratrol in an OVA-induced murine asthma model, which resulted in the upregulation of PTEN via SIRT1 activation.