Wuling San and Xiao Chaihu Decoction affect airway inflammatory response and airway smooth muscle cell proliferation in mice with allergic asthma via miR-486-5p/AQP5 axis

Objective:This study aimed to investigate the effects of Wuling San and Xiao Chaihu Decoction on allergic asthma, and elucidate the potential mechanism of Wuling San and Xiao Chaihu Decoction for ameliorating allergic asthma.

Methods:BALB/c mice were intraperitoneally injected with ovalbumin (OVA) to establish animal model of allergic asthma. Transforming growth factor beta 1 (TGF-β1) was used to induce the proliferation of airway smooth muscle cells (ASMCs) in order to establish the cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to quantify the expression levels of miR-486-5p and aquaporin-5 (AQP5) in cells and tissues. Dual-luciferase reporter assay was used to verify the targeting relationship between miR-486-5p and AQP5. MTT assay and flow cytometry were carried out to evaluate cell proliferation and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of interleukin-4 (IL-4), IL-5 and IL-13 in the bronchoalveolar lavage fluid (BALF). Hematoxylin and eosin (HE) staining and Masson staining were used to detect the recruitment of eosinophils and collagen deposition.

Results:In both in vivo and in vitro experiments, Wuling San and Xiao Chaihu Decoction significantly reduced the number of eosinophils, the levels of inflammatory factors in the BALF of asthmatic mice, and the deposition of collagen in lung tissues, and they also significantly inhibited the proliferation of ASMCs and accelerated their apoptosis (all P<0.05). Wuling San and Xiao Chaihu Decoction significantly upregulated the expression of AQP5 while inhibited the expression of miR-486-5p; additionally, miR-486-5p negatively regulated the expression of AQP5 (all P<0.05). Overexpression of miR-486-5p or silencing AQP5 can partially reverse the therapeutic effect of Wuling San and Xiao Chaihu Decoction on allergic asthma in mice and the inhibitory effect on the abnormal proliferation of ASMCs (all P<0.05).

Conclusion:Wuling San and Xiao Chaihu Decoction can influence the proliferation and apoptosis of ASMCs and the expression of inflammatory factors in mice with allergic asthma through inhibiting the expression of miR-486-5p and upregulating the expression of AQP5.

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