The Effect And Mechanism Of Amygdalin On Epithelial-Mesenchymal Transformation In The Lung Of Mice With Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory pulmonary disease characterized by continuous,progressive airflow limitation.Smoking and environmental pollution are the main causes of this.It is expected that COPD will become the world's third leading cause of death by 2020.The most important pathophysiological change of COPD is airway remodeling.It is an important reason for the restricted airflow and the progressive decline of lung function of COPD patients.However,the mechanism of airway remodeling is complex and not yet fully understood.Recent studies have shown that there are epithelial mesenchymal transitions(EMT)in the airway of patients with COPD,and EMT is closely related to airway remodeling.Inhibited or reversed the EMT process is expected to be a new target for the treatment of COPD.Amygdalin is the effective ingredient in the traditional Chinese medicine bitter almond,and its pharmacological effects are extensive.It is mainly used in cough and phlegm,immunosuppression,immune regulation,anti-inflammatory,anti-tumor and other aspects.Recent studies have shown that amygdalin can efficiently inhibit pulmonary fibrosis,liver fibrosis,renal interstitial fibrosis and other tissue fibrosis.Howere the occurrence of tissue fibrosis is closely related to EMT,we conjectured that amygdalin may inhibit EMT process.Therefore,this paper aims to study the role and the mechanism of amygdalin in the occurrence of EMT in mice with COPD.In this study,we exposured the human bronchial epithelial cell line(BEAS-2B)in cigarette smoke(CS)for 72 hours,and at the same time,we used different concentrations of amygdalin totreament,and then observed the EMT level of BEAS-2B cells.The results showed that the expression of E-cadherin,the epithelialmarker,was significantly decreased,and the expression of vimentin,the mesenchymal marker,was significantly increased,after treatment by CS.Howere,compared with CS-treated cells,E-cadherin expression of the amygdalin-treated cells,was significantly increased,and the expression of vimentin was significantly decreased.In addition,the expression of TGF-?1 and phosphorylated smad2/3(p-smad2/3),in the amygdalin-treated cells,was significantly decreased.It is indicating that amygdalin can inhibit the occurrence of EMT.And it maybe related to the inhibition of TGF-?1/smad pathway by amygdalin.Then,we bulit COPD model by passive smoking on mice and at the same time,treatment by injecting amygdalin.Three monthes liter,we observed the lung airway EMT levels by immunohistochemical staining,and measured the expression of TGF-?1,smad2,smad3,psmad2,and psmad3 in mouse lung tissue by elisa,western blot,and real-time PCR.The results showed that the expression of E-cadherin in the airway of the model group mice was significantly decreased and the vimentin was significantly increased.Howere,compared with the model group,the expression of E-cadherin was significantly increased and the vimentin was significantly decreased in the mice treated with amygdalin.In addition,the expression of TGF-?1,psmad2,and psmad3 were also decreased significantly.This indicates that there is EMT phenomenon in lung tissue of COPD mice caused by cigarette smoke,and amygdalin can delay or inhibit this process,which may be related to the inhibition of TGF-?1/smad pathway by amygdalin.