Effects Of Salvia Miltiorrhiza And Wine-Prepared Salvia Miltiorrhiza Treatment On Airway Remodeling And PI3K/AKT/mTOR Signaling Pathway Expression In Mice With Chronic Obstructive Pulmonary Disease

Objective:To explore the improvement of airway remodeling and pathological injury in mice with chronic obstructive pulmonary disease(COPD)induced by cigarette combined with lipopolysaccharidate(LPS),and to further explore their effects on the molecular expression of PI3K/AKT/mTOR signaling pathway,so as to evaluate and compare the therapeutic effects of Salvia miltiorrhiza and Wine-prepared Salvia miltiorrhiza,in order to provide a new reference for clinical treatment of COPD.Methods: One hundred C57BL/6J mice were randomly divided into Blank control group,COPD model group,Salvia miltiorrhiza treatment group(1.0g/kg),Wine-prepared Salvia miltiorrhiza treatment group(1.0g/kg),and Dexamethasone positive control group(1.0mg/kg),with 20 mice in each group.Except the Blank control group,other groups were treated with cigarette smoking combined with LPS intratracheal injection to create COPD mouse models,which lasted for 30 days.After the modeling,2 mice were randomly selected for lung function test and pathological section to confirm the success of modeling.Then the Salvia miltiorrhiza group,Wine-prepared salvia miltiorrhiza group and Dexamethasone group were given corresponding drug intervention before each smoking,and the Blank control group and the Model group were given the same volume of normal saline as the other groups by gavage,and the process lasted for 30 days.On the 60 th day of the experiment,15 mice were randomly selected from the remaining mice in each group for sampling.The right lung tissue was taken to prepare tissue homogenate and extract tissue protein.The expressions of Phosphatidylinositol 3-kinase(PI3K),Protein kinase B(AKT),Mechanistic target of rapamycin(mTOR),p-PI3 K,p-AKT and p-mTOR in lung tissue were detected by Western-blot.The left lung tissue was fixed with 4% paraformaldehyde and then pathological sections were made for hematoxylin and eosin staining(HE staining)and immunohistochemical staining.The pathological injury degree,airway remodeling and p-PI3K、p-AKT、p-mTOR protein distribution of lung tissue were observed under the microscope.Results:1.Pathological injury: Scattered inflammatory cells were infiltrated in the lung tissue of Model group mice under the pathological HE staining microscope,and the alveoli showed excessive expansion and aeration.Part of the alveoli fused with each other,and part of the airway wall structure was damaged.The degree of alveolar fusion and inflammatory cell infiltration in the Salvia miltiorrhiza group was lighter than that in the Model group,and the degree of alveolar destruction in the Wine-prepared Salvia miltiorrhiza group was lighter than that in the Salvia miltiorrhiza group.The pathological damage score of Model group was significantly higher than that of Blank control group(P < 0.01).The score of Salvia miltiorrhiza group was lower than that of Model group(P< 0.05),and the score of Wine-prepared Salvia miltiorrhiza group was lower than that of Salvia miltiorrhiza group(P < 0.05),and the differences were statistically significant.2.Airway remodeling: The bronchial structure of mice in the Blank control group was complete,while some bronchial structures of mice in the other groups were not structured,and the fibrous columnar epithelium was necrotic and exfoliated to varying degrees.The bronchial wall and bronchial smooth muscle were thickened in different degrees.The thickening of smooth muscle layer was the most obvious in the model group,followed by the Salvia miltiorrhiza group,and the smooth muscle layer thickened slightly in the Wine-prepared Salvia miltiorrhiza group.3.Protein expression measurement:The protein expression levels of PI3 K,AKT and mTOR were not significantly different among the five groups,but the phosphorylated protein p-PI3 K,p-AKT and p-mTOR were most significantly increased in the model group,followed by the Salvia Miltiorrhiza group,the Wine-prepared Salvia miltiorrhiza group,Dexamethasone group and Blank control group,and the difference was statistically significant.Conclusion:1.PI3K/AKT/mTOR signaling pathway is involved in the development of COPD.2.Salvia miltiorrhiza and Wine-prepared salvia miltiorrhiza can alleviate pathological injury and improve airway remodeling in mice with COPD,and the effect of the Wine-prepared Salvia miltiorrhiza treatment is more obvious.3.Salvia miltiorrhiza and Wine prepared Salvia Miltiorrhiza can inhibit the expression of PI3K/AKT/mTOR signaling pathway,and the effect of Wine prepared Salvia Miltiorrhiza is more obvious.