| Research background and purpose:Asthma is a common chronic nonspecific inflammatory airway disease.The mechanism of airway inflammation involves different types of cells,metabolites and signal molecular transmission pathways.Lipids are closely related to respiratory diseases.Recognizing lipid biomarkers has important scientific significance for the early diagnosis and treatment of diseases.Triglycerides are the most abundant lipids in the circulation and are closely related to inflammation.Diacylglycerol acyltransferase 1(DGAT1)is a key step in triglyceride synthesis in airway epithelial cells.At present,the relationship between blood lipids and asthma has not been clarified.This project intends to further explore the following issues through clinical research,animal experiments in vivo and cell experiments in vitro.1.Whether there is a correlation between asthma and blood lipids.2.The role of triglyceride metabolism in airway inflammation in asthma and its possible mechanisms.Research method:1.Clinical trials:1.1 Collect 49 asthma patients and 45 normal people with height,weight,age,blood lipids,blood routine,and lung function results.1.2 The independent sample T test analyzes the differences in age and BMI between the asthma group and the control group.The chi-square test verifies the gender differences,and M-W tests the differences in age and BMI.1.3 The M-W test analyzes the differences between groups in blood lipids,white blood cell classification count,and lung function.Linear regression analysis of the relationship between blood lipids,white blood cell counts,and lung function in patients with asthma.2.In vivo experiment:2.1 C57BL/6 mice were randomly divided into control group,HDM group,HDM+DGAT1 inhibitor group.All mice were treated accordingly for 4 consecutive weeks.2.2 Collect mouse blood for classification and count of white blood cells,and detect inflammatory factors and triglyceride levels in serum and lymphocyte culture supernatant.2.3 Collect lung tissues for HE staining and immunohistochemical staining of DGAT1 molecules.3.In vitro experiment:3.1 The CCK8 experimental method was used to test the effect of A922500,the DGAT1 inhibitor,on the activity of HBE cells.3.2 Detect the expression of DGAT1 and intracellular triglyceride levels in HBE cells in each group.3.3 Detect the expression of IL-25 and TSLP in HBE cells by Western Blot.3.4 Detects the phosphorylation level of STAT5 and AKT in HBE cells by Western Blot.Research result:1.TC,LDL,HDL and VLDL were not significantly different between the control group and the asthma group.However,the level of plasma triglycerides in the asthma group was lower than that in the control group,and it was significantly positively correlated with lymphocyte count.2.The levels of triglycerides of mice with asthma were lower in the plasma and higher in the lung tissues than those of the control group.A922500 can reduce triglyceride levels in mouse plasma and lung tissue.The expression of DGAT1 in the airway epithelium,the infiltration of inflammatory cells around the airway,and the levels of IL-5 and IL-13 in the lung tissue of asthmatic mice were significantly higher than those in the control group,which are significantly reduced after the treatment of A922500.3.A922500 reduces the higher expression of DGAT1,IL-25 and TSLP in the HDM-induced HBE cells,and at the same time inhibits the phosphorylation of STAT5 and AKT.Analysis conclusion:Asthma patients and mouse models have disorders of triglyceride metabolism,inhibiting triglyceride synthesis can reduce airway inflammation in asthmatic mice,whose mechanism may be mediated by inhibiting the STAT5/AKT signaling pathway. |
