Abstract:

Objective To discuss the expressions of autotaxin （ATX） and lysophosphatidic acid receptor 3 （LPA3） in serum and lung tissue of the chronic obstructive pulmonary disease （COPD） patients， and to clarify the role of ATX and LPA3 in the occurrence and development of COPD. Methods A total of 40 COPD patients were collected and brought into acute exacerbation of COPD group （AECOPD group）； after treatment， those stabilized patients were included in COPD stable group （n=40）； additionally， 40 healthy individuals were recruited as control group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the ATX levels in the serum of the subjects in various groups. Another 80 patients who underwent lobectomy were divided into COPD smoking group （CS group， n=20）， COPD non-smoking group （CNS group， n=20）， non-COPD smoking group （HS group， n=20）， and non-COPD non-smoking group （HNS group， n=20）. The general informations of the subjects in various groups were collected. HE staining was used to observe the pathomorphology of lung tissue of the patients in various groups；immunohistochemical staining was used to detect the expression levels of ATX and LPA3 proteins in lung tissue of the patients in various groups；real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of ATX and LPA3 mRNA in lung tissue of the patients in various groups；Pearson correlation analysis was used to evaluate the correlations of continuous variables with normal distribution， and Spearman correlation analysis was used to evaluate the correlations of other variables. Results Compared with control group， the percentage of forced expiratory volume in the first second to predicted value （FEV1%pred） and the percentage of forced expiratory volume in the first second to forced vital capacity （FEV1/FVC） of the patients in COPD stable group were significantly decreased （P<0.05）. Compared with COPD stable group and control group， the level of ATX in serum of the patients in AECOPD group was increased （P<0.05）； compared with control group， the level of ATX in serum of the patients in COPD stable group was increased （P<0.05）. The serum ATX level of the patients in AECOPD group was positively correlated with COPD Assessment Test （CAT） scores （r=0.581， P<0.001） and showed no correlations with smoking history， white blood cells （WBC）， percentage of neutrophils （NEUT%）， neutrophil to lymphocyte ratio （NLR）， and body mass index （BMI） （P>0.05）. The serum ATX level of the patients in COPD stable group was positively correlated with WBC and CAT score （r=0.384， P=0.014； r=0.463， P=0.003） and negatively correlated with FEV1%pred and FEV1/FVC （r=-0.393， P=0.012； r=-0.353， P=0.025）. Compared with CS group and CNS group， the FEV1%pred and FEV1/FVC of the patients in HS group and HNS group were increased （P<0.05）. The immunohistochemical staining results showed that compared with CS group， the expression levels of ATX and LPA3 proteins in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）. Compared with CNS group， the expression levels of ATX and LPA3 proteins in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）. The RT-qPCR results showed that compared with CS group， the expression levels of ATX and LPA3 mRNAs in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）； compared with CNS group， the expression levels of ATX and LPA3 mRNAs in lung tissue of the patients in HS group and HNS group were decreased （P<0.05）. The correlation analysis results showed that the expression level of ATX protein in lung tissue of the COPD patients was positively correlated with the expression level of LPA3 protein （r=0.723， P<0.001）. Conclusion The expression levels of ATX and LPA3 mRNA and proteins in lung tissue of the COPD patients are increased. The serum ATX levels in both AECOPD group and COPD stable group are increased， suggesting that these factors may be involved in the inflammatory response of COPD， promoting its occurrence and development.

Key words: Chronic obstructive pulmonary disease, Autotaxin motility factor, Lysophosphatidic acid, Receptor, Smoking