Based on the Theory of"Lung Channel Regulation",the regulatory Mechanism of CFTR-Mediated Imbalance of Infingolipid Metabolism on Chronic Obstructive Pulmonary Disease was Investigated
Objective The material basis and pathway of CFTR regulation of sphingolipid metabolism in COPD were discussed,and the theory of lung channel regulation was further elucidated.Methods The mouse model of COPD was established by smoking method,and the CFTR model was established by smoking plus CFTR agonist.The pathological changes of lung tissues were observed and the mouse model was evaluated.Ceramide and sphingosine-1-phosphate expression of sphingolipid metabolites in plasma of the model were detected by LC-MS mass spectrometry.Western blot was used to detect the phosphorylation levels of Sphks,ASM and CFTR proteins in the lung tissue of the mouse model.Quantitative fluorescence PCR was used to detect the mrna transcription levels of Sphks,Smpd and CFTR mRNA in the lung tissue of the mouse model.Results The expression of S1p in COPD group and CFTR intervention group was lower than that in control group(P<0.05),and the expression of S1P in CFTR intervention group was higher than that in COPD group(P<0.05).The protein phosphorylation levels of CFTR and Sphk1 were low in COPD group and CFTR intervention group,the lowest expression in COPD group was different from that in control group and CFTR intervention group(P<0.05),and Sphk2 was different in COPD group and control group(P<0.05).ASM in COPD group and CFTR intervention group was higher than that in control group(P<0.05).CFTR mRNA in COPD group and CFTR intervention group was lower than that in control group,and there were differences between COPD group and control group(P<0.05).Sphk1 mRNA expression was the highest in control group,and there were differences between it and COPD group and CFTR intervention group(P<0.05).SMPD1 mRNA was highly expressed in COPD group and CFTR intervention group,and was different from control group(P<0.05).Conclusion To explore the material changes of pulmonary aqueduct dysfunction in COPD diseases,and to reveal the pathway of CFTR affecting water and fluid metabolism in COPD by participating in the regulation of sphingolipid metabolism.
Chronic obstructive pulmonary diseaseCFTRSphingolipidLung regulates the water channel