Correlation Analysis Of IGF-1 Level And Other Inflammatory Factors In Mice With Obesity Asthma

Objective: To establish the mice model of obese asthma and common asthma,and to detect the levels of insulin-like growth factor-1(IGF-1),leptin,IL-6 and IgE in serum and BALF of mice,and then to analyze the correlation between inflammatory factors,so as to preliminarily explore the possible effect and role of IGF-1 on airway mucus hypersecretion and inflammation in obese asthma.Methods: Sixty SPF mice in 3 weeks' old were bought from Charles River.They were fed adaptively for 1 week before the experiment,and then divided into 4 groups: control group,obese group,asthma group and obese asthma group.The weight of each group of mice was weighed.Mice in obese group and obese asthma group were fed with high-fat diet,and the fat energy supply ratio of high-fat diet was 45%.The control group and asthma group were fed with ordinary feed,and the fat ratio of ordinary feed was about 10%.The mice were fed adaptively for one week.During the experiment,the body length and weight of mice need to be measured weekly.Obese model was established by feeding high-fat diet,asthma model was established by intraperitoneal injection and atomization inhalation of ovalbumin,while normal feed,intraperitoneal injection and atomization inhalation were given to control group and obese group respectively.After the final atomization inhalation was completed,experimental specimens of mice were collected.And test the weight of all mice.The levels of insulin-like growth factor-1(IGF-1),immunoglobulin E(IgE),interleukin-6(IL-6)and leptin in serum and alveolar lavage fluid(BALF)of four groups of mice were measured by enzyme linked immunosorbent assay(ELISA).The total number of white blood cells and the classified count of inflammatory cells in BALF of mice in each group were detected respectively,and the inflammation of airway and alveolus was observed.After HE staining of mice lung tissue specimens,the phenomenon and degree of remodeling in airway and alveoli of mice in each group and the oversecretion of mucus were observed.The mRNA levels of Munc18 b and Muc5 ac in lung tissue samples were measured by real-time quantitative PCR(RealTime-PCR).Results: At the end of 8 weeks,the weight of obese asthma group and obese group washigher than that of control group and asthma group(P < 0.05).After several minutes,the respiratory frequency and depth of the mice in asthma group and obese asthma group increased significantly,and then the behavior of the mice was obviously active,accompanied by symptoms of acute attack of asthma such as dysphoria.After that,the mice were depressed,the activity amount was obviously reduced,and the food intake and frequency were also obviously reduced.No obvious abnormality was found in obese group and control group mice.Moreover,obese asthma group is heavier than asthma group.The total number of leukocytes,eosinophils and neutrophils in obese asthma group were significantly higher than those in control group,obese group and obese asthma group(P < 0.05),while those in asthma group were higher than those in control group and obese group(P < 0.05).The levels of serum IGF-1 and leptin in obese asthma group,asthma group and control group were significantly higher than those in control group(P < 0.05),and the levels of IGF-1 and leptin in obese asthma group were higher than those in asthma group(P < 0.05).The levels of IGF-1,IL-6 and IgE in BALF of obese asthma group,asthma group and obese group were significantly higher than those of control group(P < 0.05).Moreover,the levels of IGF-1,IL-6 and IgE in obese asthma group were higher than those in asthma group,and the difference was statistically significant(P < 0.05).The level of serum IGF-1 was positively correlated with leptin(P < 0.05),and the level of BALF IGF-1 was also positively correlated with IL-6 and IgE(P < 0.05).HE staining of lung tissue showed that the bronchial epithelial mucosa of obese asthmatic mice was edematous to different degrees,the bronchial wall also had obvious thickening,the inflammatory cells in the bronchial wall and alveolus also increased with infiltration,and the mucus secretion in the lumen and alveolar cavity also increased.Among them,the pathological manifestations of obese asthma group are more obvious.Obese group has certain inflammatory changes,while the control group has basically no obvious changes.The results of RT-PCR showed that the expression levels of Munc18 b and Muc5 ac mRNA in obese asthma group were significantly higher than those in all other groups(P < 0.05),and the expression levels of asthma group were higher than those in control group and obese group(P < 0.05).Conclusion: 1.The infiltration of inflammatory cells in the airway of mice with obesity asthma group was significantly higher than that of normal asthma group.2.IGF-1 is one of the important inflammatory factors in airway inflammation and mucus secretion in obese asthmatic mice,and is positively correlated with leptin,IgE and IL-6.The expression levels of STAT3,Munc18 b and Muc5 ac mRNA in the lung tissues of mice withobese asthma were significantly higher than those of the simple asthma group by Western-blot analysis.Therefore,it was speculated that the STAT3-Munc18B-MUC5 AC pathway may be one of the mechanisms of airway mucus hypersecretion in obese asthma.