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清肺口服液通过 mTOR 信号通路抑制自噬来减轻 RSV 感染哮喘小鼠的炎症。

Qingfei oral liquid inhibited autophagy to alleviate inflammation via mTOR signaling pathway in RSV-infected asthmatic mice.

机构信息

Department of Traditional Chinese Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China.

Department of Traditional Chinese Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China.

出版信息

Biomed Pharmacother. 2021 Jun;138:111449. doi: 10.1016/j.biopha.2021.111449. Epub 2021 Mar 8.

Abstract

Qingfei oral liquid (QF) is a traditional Chinese medicine that has been used to treat patients with viral pneumonia and asthma for decades. Our previous study revealed that QF prevents airway inflammation and reduces airway hyperresponsiveness (AHR) in respiratory syncytial virus (RSV)-infected asthmatic mice. RSV infection can exacerbate asthma in pediatric patients and induce autophagy, which leads to the promotion of inflammatory cytokine production in the pathology of this disease. The effect of QF on regulating autophagy in RSV-infected asthma patients has not been fully elucidated. In this study, we identified compounds of QF by HPLC-DAD-Q-TOF-MS/MS. The RSV infected OVA challenged mice, we evaluated the RSV-infected asthma model. We found that treatment with QF alleviated airway inflammation and mitigated airway AHR in RSV-infected asthmatic mice. In addition, we found that QF inhibited autophagosome formation and the expression of LC3 protein by using electron and laser confocal microscopy, respectively, to assess RSV-infected asthmatic mice lung tissues. Furthermore, QF was found to reduce the quantity of autophagy and its related proteins LC3B (light chain 3B), Beclin-1, p62 and Atg5 (autophagy-related gene 5) and downstream inflammatory cytokines TNF-α, IL-4, IL-6, and IL-13 via an action in mTOR-dependent signaling in vivo and in vitro. These findings suggest that QF can alleviate the inflammation caused by RSV infection in asthmatic mice, and its mechanism may be involved in the regulation of autophagy via the mTOR signaling pathway.

摘要

清肺口服液(QF)是一种中药,已被用于治疗病毒性肺炎和哮喘患者数十年。我们之前的研究表明,QF 可预防呼吸道合胞病毒(RSV)感染的哮喘小鼠的气道炎症和降低气道高反应性(AHR)。RSV 感染可使儿科患者的哮喘恶化,并诱导自噬,从而促进该疾病病理中的炎症细胞因子产生。QF 对调节 RSV 感染的哮喘患者的自噬作用尚未得到充分阐明。在这项研究中,我们通过 HPLC-DAD-Q-TOF-MS/MS 鉴定了 QF 的化合物。我们评价了 RSV 感染的哮喘模型。我们发现,QF 治疗可减轻 RSV 感染的哮喘小鼠的气道炎症和减轻气道 AHR。此外,我们发现 QF 通过电子和激光共聚焦显微镜分别抑制 RSV 感染的哮喘小鼠肺组织中的自噬体形成和 LC3 蛋白的表达。此外,QF 通过体内和体外的 mTOR 依赖性信号通路被发现减少自噬及其相关蛋白 LC3B(轻链 3B)、Beclin-1、p62 和 Atg5(自噬相关基因 5)和下游炎症细胞因子 TNF-α、IL-4、IL-6 和 IL-13 的数量。这些发现表明,QF 可以减轻 RSV 感染引起的哮喘小鼠的炎症,其机制可能涉及通过 mTOR 信号通路调节自噬。

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