Serum Level Of Netrin-1 In Patients With Chronic Obstructive Pulmonary Disease

Background:The main pathological feature of Chronic obstructive pulmonary disease(COPD)is characterized by chronic inflammation,mucosal metaplasia,alveolar structural destruction and the essence of cell apoptosis.Inflammation and oxidative stress are often thought to be the major pathogenesis of COPD.The diagnosis of COPD mainly depend on the clinical manifestation and lung function,but some patients with pulmonary bullae,cardiac insufficiency are not suitable for pulmonary function test.Therefore,it's very important to exploring the related serological biomarkers for the diagnosis and monitor of COPD.Axon guidance factor-1(Netrin-1)is a kind of laminin related secreted protein,which has high expression in the nervous system of many species.It has shown in recent studies that netrin-1 and its receptors are also expressed in lung tissues and negatively modulate the transmission of inflammatory signals.Objective:To compare the serum levels of netrin-1 and its clinical significance in patients with different stages of COPD.Methods:The peripheral blood of 20 COPD patients of acute exacerbation stage,46 COPD patients of stable stage and 23 healthy subjects are collected.We used ELISA method to measure the concentration of netrin-1 in serums,and compare the difference among various groups.The multiple linear regression is adopted to analyze the possible factors affecting the level of netrin-1 and investigate the correlation between netrin-1 and lung function.Ozone-treated COPD mouse model was used to verify the expression and distribution of Netrin-1 on the lung.Results:Compared with the healthy control group(59.87+7.160pg/m),serum netrin-1 in stable phase COPD(142.5+13.94 pg/m,P<0.01)and acute exacerbation of COPD(207.4+38.93 pg/ml,P<0.01)increased gradually.The CAT scale rating was adopted for grading the patients of stable COPD.The netrin-1 levels of CAT(11-20)and CAT(21-30)patients are significantly higher than that of the CAT(<10)patients and the healthy control group(P<0.05).The serum netrin-1 level was negatively correlated with lung function(FEV1,FEV1%,FVC)(P<0.05).We also found that the serum netrin-1 level is closely related to smoking.Compared with nonsmokers of COPD patients,the netrin-1 level in the serum of the smokers of COPD patients is significantly higher(P<0.01).It was found that netrin-1 was mainly distributed in bronchial epithelial cells by performing immunohistochemical staining of COPD lung tissues,and its expression increased significantly compared with the control group.The above phenomena were also confirmed in the lung tissue of ozone-treated mouse.Conclusions:Netrin-1 in serum is associated with the severity,grade,stage,and smoking,and may be a potential biomarker for COPD.