关键词: 虫草素, 哮喘, 上皮细胞间充质转化, 支气管, 人支气管上皮样细胞

Abstract: Objective To investigate the mechanism of cordycepin (Cor) in the inhibition of epithelial-mesenchymal transition in asthmatic rats. Methods Rats were randomly divided into 4 groups (n=10): control group, ovalbumin (OVA) group, OVA+10 mg/kg Cor group, OVA+50 mg/kg Cor group. After 7 days of treatment, the cell counting in bronchoalveolar lavage fluid (BALF) was measured; hematoxylin-eosin (HE) staining was used to evaluate airway inflammation and airway remodeling. Masson's trichrome staining was used to detect epithelial collagen deposition. Human bronchial epithelioid cells 16HBE were divided into 3 groups: control group, TGF-β1 group and TGF-β1+Cor group. Immuno-fluorescence staining was used to detect the expression of c-Jun in the cells. Cell proliferation and migration were examined by cell counting kit-8 (CCK-8) and Transwell. The protein expression of E-cadherin, N-cadherin, α-SMA, vimentin, Smad3, p-Smad3, ERK1/2 and p-ERK1/2 was detected by immuno-histochemical staining or Western blot. Results With comparison with specific control groups, the following results were recorded. The collagen fiber area and cell count of OVA group increased significantly(P＜0.05). The collagen fiber area and cell count of OVA+10 mg/kg Cor group and OVA+50 mg/kg Cor group both decreased (P＜0.05). E-cadherin staining degree and protein expression of OVA group decreased, while the staining degree of α-SMA increased and the protein expression of N-cadherin, α-SMA and vimentin increased (P＜0.05); E-cadherin staining degree and protein expression of OVA+10 mg/kg Cor group and OVA+50 mg/kg Cor group increased, while the staining degree of α-SMA decreased and the protein expression of N-cadherin, α-SMA and vimentin decreased (P＜0.05). Compared with control group, the cell viability and the number of migrating cells in the TGF-β1 group increased (P＜0.05); compared with the TGF-β1 group, the cell viability and the number of migrating cells in the TGF-β1+Cor group were both decreased (P＜0.05). The expression level of E-cadherin protein in TGF-β1 group decreased, while the protein expression of N-cadherin, α-SMA, vimentin, p-Smad3 and p-ERK1/2 increased (P＜0.05). The E-cadherin protein expression level of TGF-β1+Cor group increased, while the N-cadherin, α-SMA, vimentin, p-Smad3 and p-ERK1/2 protein expression levels decreased (P＜0.05). The relative fluorescence intensity of c-Jun in TGF-β1 group increased (P＜0.05); The relative fluorescence intensity of c-Jun in TGF-β1+Cor group decreased (P＜0.05). Conclusions Cordycepin inhibits EMT in asthma by inhibiting Smad3 and ERK1/2 signaling pathway and c-Jun.

Key words: cordycepin, asthma, epithelial-mesenchymal transition, bronchus, human bronchial epithelioid cells