Effects Of Obesity On Lung Function,Expression Of HSPA8 In Lung Tissue And Lung Inflammation

Part Ⅰ Correlation between body mass index and lung function in patients with chronic obstructive pulmonary diseaseObjective:To explore the correlation between body mass index and main indicators of lung function in patients with stable chronic obstructive pulmonary disease.Methods:We collected Information on lung function,age,gender,height and weight of patients with stable COPD admitted to our hospital from September 2020 to September 2022,and calculated body mass index.The patients were divided into low body mass index group(BMI<18.5 kg/m2)、normal body mass index group(18.5kg/m2≤BMI<25 kg/m2)、high body mass index group(BMI≥25kg/m2)based on BMI.Pearson correlation analysis in SPSS 26.0 software was used to analyze the correlation between BMI and main indicators of lung function;Compare the differences in lung function indicators among different BMI groups.Results:1.A total of 207 patients with stable COPD were included,there are 139 males and68 females;Patients were divided by BMI: 29 in the low BMI group,119 in the normal BMI group,59 in the high BMI group.Among all the included patients,the highest BMI was 33.12 kg/m2,which was within the range of Grade 1 obesity.There was no statistically significant difference in the ratio of male to female and age distribution among the groups.2.Pearson correlation analysis show that BMI was positively correlated with FVC,FEV1/FVC and MMEF,and the correlation between BMI and FEV1/FVC was the strongest.3.Among different BMI groups,the FVC of high BMI group was higher than that of normal BMI group and low BMI group,and the difference was statistically significant.The FEV1/FVC and MMEF in the high BMI group and the normal BMI group were higher than those in the low BMI group,and the difference was statistically significant.Conclusions: 1.BMI was positively correlated with FVC,FEV1/FVC and MMEF,and the correlation with FEV1/FVC was the most significant.2.Below grade 1 obesity,higher BMI is associated with better lung function.Part Ⅱ Bioinformatics method screened the central differential gene from mice on high fat diet and control diet: based on GEO databaseObjective:To screened the differentially expressed central genes in lung tissues of mice on high fat diet and control diet from GEO database by bioinformatics analysis methods.Methods:1."high fat diet","obesity" and "lung" were used as search terms in GEO database,then Download the gene expression dataset from mouse lung tissue contained a high-fat diet and a control diet.2.The Limma package of R language was used to analyze the differential genes in the data set and the intersection of differential genes was visualized by Venn diagram.3.PPI network analysis was carried out on the common differential genes via the STRING website.cyto Hubba plug-in in Cytoscape software was used to calculate the network node scores.4.The top 15 central genes were selected for GO and KEGG pathway enrichment anlysis.5.MGI database was used for further analysis of target central genes.Results: 1.Data sets GSE16377 and GSE38093 containing gene expression data in lung tissues of mice on high-fat diet and control diet were retrieved through GEO database.GSE16377 contained 3 high-fat diet samples and 3 control diet samples,GSE38093 contained 8 high-fat diet samples and 8 control diet samples.2.81 common differentially expressed genes were obtained by intersection of the two data sets.3.The top 15 genes were identified by protein interaction analysis and Cytoscape as HSPA8,BTK,HSPA1 B,CYCS,CCR7,CIDEC,HSPA1,TNFSF10,ADIPOQ,CD22,CDKN1 A,ACADM,AOC3,DNAJA1,HSPH1,among which HSPA8 had the highest score as the target central gene.4.The first 15 central genes are involved in different biological processes and was enriched in protein refolding in biological process pathways.The cell composition pathway was concentrated in the membrane microregion.The molecular functional pathway was enriched in binding unbound proteins;The KEGG pathway was enriched in protein processing in the endoplasmic reticulum.5.The analysis of HSPA8 in MGI database showed that it could be expressed in various systems and tissues in vivo,which was homologous with human HSPA8.The biological pathways are mainly concentrated in carbohydrate derivative metabolism,nucleic acid transcription,protein metabolism and stress.The cell composition are enriched in cytoplasm and nucleus.The molecular functions are mainly concentrated in carbohydrate derivative binding,lipid binding,ribonucleic acid binding.Conclusions: 1.High-fat diet can lead to differential expression of lung tissue genes;2.HSPA8 was the differentially expressed central gene in high-fat diet and control diet.3.HSPA8 was widely expressed in vivo and involved in a variety of biological processes.Part III Effects of obesity and weight loss on the expression of HSPA8 in lung tissue,lung inflammation and fiber depositionObjective:Through the establishment of high fat diet induced obesity model and weight loss model in mice,to explore the effects of obesity induced by high fat diet and weight loss in mice on the expression of HSPA8,pulmonary inflammation and fiber deposition.Methods: Forty-eight C57BL/6 mice were randomly divided into 4 groups,which were normal control diet group(N),high fat diet group(H),diet control group(D),diet control combined with swimming exercise group(D+E).The obesity mouse model was constructed by high fat diet method,diet control method and diet control combined with swimming exercise method.The success of the model was determined by measuring the body mass and serum triglyceride and total cholesterol.After the successful establishment of the model,the expression levels of HSPA8 and inflammatory factors in lung tissues of mice in each group were detected by immunohistochemistry,and the average optical density was used for semi-quantitative analysis.HE staining was used to observe the inflammatory infiltration in lung tissue of mice in each group.Finally,the collagen fiber deposition in lung tissues of mice in each group was observed by Masson staining.Results: 1.After feeding high fat diet for 16 weeks,the body weight of group H was significantly higher than that of group N,and after losing weight for 3 weeks,the body weight of group D and D+E were significantly lower than that of group H.2.At the end of the 19 th week,total cholesterol and triglyceride in group H were significantly higher than those in groups N,D and D+E,and there was no significant difference in serum total cholesterol and triglyceride levels among groups N,D and D+E.3.Compared with group N,the expression level of HSPA8 in group H was significantly increased,and after weight loss,the expression level of HSPA8 in group D and D+E was significantly decreased compared with group H,and there was no significant difference in the level of HSPA8 among group N,D and D+E.4.Compared with group N,the levels of inflammatory factors in lung tissue of group H were increased and inflammatory infiltration was obvious.The inflammatory infiltration in group D and group D+E was improved to some extent,and the improvement effect was better in group D+E.5.Masson staining results showed that the collagen fiber deposition in lung tissues of group H was more obvious than that in group N,and the collagen deposition in lung tissues of group D and D+E was less than that in group H.Conclusions: 1.The mouse obesity model can be established by high-fat diet,and the mouse weight loss model can be established by diet control or diet control combined with swimming exercise;2.The expression of HSPA8 in lung tissue of obesity induced by high fat diet was increased and could be restored to normal level after weight loss.3.Obesity induced by high fat diet can cause lung tissue inflammatory infiltration and lung fiber deposition;After weight loss,the inflammatory infiltration and fiber deposition of lung tissue were improved to some extent,and diet control combined with exercise had better effect.