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丹皮酚通过抑制TLR4/NF-κB和MAPK信号通路改善卵清蛋白诱导的哮喘。

Paeonol Ameliorates Ovalbumin-Induced Asthma through the Inhibition of TLR4/NF-B and MAPK Signaling.

作者信息

Tang Yongjun, Huang Weihua, Song Qianqian, Zheng Xiangrong, He Ruohui, Liu Jie

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, China.

出版信息

Evid Based Complement Alternat Med. 2018 Aug 15;2018:3063145. doi: 10.1155/2018/3063145. eCollection 2018.

Abstract

Asthma is a chronic inflammatory disease of the airways, with complex signaling pathways involved in its pathogenesis. It was reported that paeonol attenuated airway inflammation of ovalbumin (OVA)-induced mice. Therefore, it is of importance to further investigate the underlying mechanism. BALB/c mice were challenged with OVA for the asthma model, which was validated by the changed levels of IL-4, IFN-, and IgE. The elevation of IL-4 and the decreasing of IFN- were significantly in middle (p<0.05) or high (p<0.01) paeonol dose groups compared with OVA group. MIP-1 in bronchoalveolar lavage fluid (BALF) also decreased significantly in middle and high paeonol group compared with OVA group (p<0.01), which is similar to the change of its mRNA in lung tissues. Moreover, the inflammatory cells infiltration and collagen deposition were attenuated by paeonol and montelukast sodium via histology examination. At last the immune blot of the protein extracted from lung tissues demonstrated that paeonol decreased the expression of TLR4 and the nuclear translocation of NF-B, as well as the phosphorylation levels of P38 and ERK in asthma model. In conclusion, paeonol ameliorated OVA-induced asthma through the TLR4/NF-B and mitogen-activated protein kinase (MAPK) signaling.

摘要

哮喘是一种气道慢性炎症性疾病,其发病机制涉及复杂的信号通路。据报道,丹皮酚可减轻卵清蛋白(OVA)诱导的小鼠气道炎症。因此,进一步研究其潜在机制具有重要意义。用OVA对BALB/c小鼠进行攻击以建立哮喘模型,通过IL-4、IFN-和IgE水平的变化进行验证。与OVA组相比,中剂量(p<0.05)或高剂量(p<0.01)丹皮酚组中IL-4升高而IFN-降低。与OVA组相比,中、高剂量丹皮酚组支气管肺泡灌洗液(BALF)中的MIP-1也显著降低(p<0.01),这与其在肺组织中mRNA的变化相似。此外,通过组织学检查发现,丹皮酚和孟鲁司特钠可减轻炎症细胞浸润和胶原沉积。最后,对从肺组织中提取的蛋白质进行免疫印迹分析表明,在哮喘模型中,丹皮酚降低了TLR4的表达、NF-κB的核转位以及P38和ERK的磷酸化水平。总之,丹皮酚通过TLR4/NF-κB和丝裂原活化蛋白激酶(MAPK)信号通路改善OVA诱导的哮喘。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/919a/6114069/0b8334c384c2/ECAM2018-3063145.001.jpg

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