| Objective:To observe the expression of HIF-1a and TGF-?1 in asthmatic rats and their relationship with airway remodeling in asthmatic rats,and to explore the possible mechanism of azithromycin on airway remodeling in asthmatic rats.Methods: thirty-two male Sprauge-Dawley(SD)rats were randomly divided into normal control group(group A),asthma group(group B),asthma+azithromycin group(group C),asthma+dexamethasone group(group D),8 rats in each group.asthma group: the rats were sensitized intraperitoneally with the mixture of ovalbumin and aluminum hydroxide 1ml respectively in first days and eighth days,each nose of rats was dripped into 2mg·ml-1 OVA 40 ul daily after being anesthesia intraperitoneally with 40mg·kg-1 1% pentobarbital sodium for 28 consecutive days.it would be successful if the rats with shortness of breath,sneezing,cyanosis,convulsions,wheezing,irritability and other symptoms.asthma+azithromycin group:the initial preparation was the same as asthma group,sarting from nasal provocation,rats in group C were injected intraperitoneally with azithromycin injection 50mg·kg-1 every day 30 min ago before intranasal provocation,and azithromycin injection was injected 1 times a day for 28 days.asthma+dexamethasone group:the initial preparation was the same as asthma group.sarting from nasal provocation,rats in group D were injected intraperitoneally with dexamethasone injection 0.5mg·kg-1 every day 30 min ago before intranasal provocation,and dexamethasone injection was injected 1 times a day for 28 days.normal control group:rats in group A were injected intraperitoneally with 1ml normal saline for first day and eighth day.rats in group A were injected intraperitoneally with 1ml normal saline before being given 1ml normal saline to intranasal provocation,1 times a day for 28 days.Twenty-four hours after the final intranasal challenge,the rats in each group were anesthetized and the right lung tissues of the rats were collected,the rats airway pathological changes were observed by Hematoxylin Eosin(HE)staining;parameters of airway remodeling were determined by medical image analysis system.Immunohistochemistry was used to detect the expression HIF-1a and TGF-?1 in lung tissue,and ELISA was used to detect the expression of HIF-1a and TGF-?1 in serum.Results: 1.general situation: at the beginning of the experiment,rats of each group acted quickly,fun and appetite.during the experiment,the rats of group B suffered from poor appetite and weight loss,and there were symptoms such as restlessness,sneezing,shortness of breath,wheezing after stimulation,some of the rats could be heared wheezing sounds.the rats in group C and D also suffered from poor appetite and weight loss,and there were symptoms such as restlessness,sneezing,shortness of breath,wheezing after stimulation,but all of the rats could not be heared wheezing sounds.after fourteenth days of stimulation,No.7 rat of group C died after anesthesia and provocation,it may be caused by overdose of anesthesia and asthma provocation.the rats' weight of group A increased during the experiment,there was no obvious abnormal behavior and appetite,and no symptoms such as wheezing or sneezing.2.HE staining of lung tissue in each group:group A had normal tracheal structure at all levels,bronchial epithelium was continuous and complete,no mucosal abscission and inflammatory cell infiltration.Compared with group A,group B showed local mucosal epithelial necrosis and shedding,the mucus suppository is visible in the bronchus,goblet cells increased,mucus gland hyperplasia,bronchial wall thickening,the smooth muscle cells of the tube wall proliferation and hypertrophy,a large number of inflammatory cells were infiltrated in the airway wall and lung tissue,mainly lymphocytes,eosinophils,but it was less than that in group B.3.Airway remodeling parameters of lung tissue:the thickness of bronchial wall and the thickness of smooth muscle in group B was higher than that in group A(P<0.05),there was no obvious abnormality in group C and D compared with group A(P>0.05),the thickness of bronchial wall in group C and group D were lower than that in group B(P<0.05),and the thickness of smooth muscle in group C and group D was not significantly abnormal compared with that of group B(P>0.05).4.Immunohistochemical detection of the expression of HIF-1a and TGF-?1 in lung tissue:the expression of HIF-1a in lung tissue of rats in group B?group C and group D was significantly higher than that in group A(P<0.05),no significant changes were found between the three groups(P>0.05);the expression of TGF-?1 in lung tissue of group B was significantly higher than that in group A(P<0.05),group C and D was lower than that in group B(P<0.05),group C and group D was not significantly different from that in group A(P>0.05).5.ELISA was used to detect the content of HIF-1a and TGF-?1 in the serum of rats:the content of HIF-1a in serum of rats in group B?group C and group D was significantly higher than that in group A(P<0.05),no significant changes were found between the three groups(P>0.05);the content of TGF-?1 in serum of group B was significantly higher than that in group A(P<0.05),group C and D was lower than that in group B(P<0.05),group C and group D was not significantly different from that in group A(P>0.05).6.The correlation analysis of HIF-1a,TGF-?1,bronchial wall thickness and smooth muscle thickness in rats :there was a positive correlation between HIF-1a and TGF-?1 in the lung tissue of rats(r=0.426,P<0.05),there was a positive correlation between HIF-1a and TGF-?1 in rat serum(r=0.608,P<0.01),there was a positive correlation between the HIF-1a in the lung tissue and the thickness of the bronchial wall of rats(r=0.676,P<0.01),there was a positive correlation between the TGF-?1 in the lung tissue and the thickness of the bronchial wall of rats(r=0.359,P<0.05).there was a positive correlation between the TGF-?1 in the serum and the thickness of the bronchial wall of rats(r=0.561,P<0.01).there was a positive correlation between the TGF-?1 in the serum and the thickness of smooth muscle of rats(r=0.433,P<0.05).there was a positive correlation between the thickness of the bronchial wall and the thickness of the smooth muscle of the rats(r=0.793,P<0.01).Conclusions:1.The expression of HIF-1a and TGF-?1 increased in asthmatic rats and was involved in airway remodeling in asthma.2.Azithromycin can improve symptoms and relieve airway remodeling in asthma.it can not improve airway remodeling in asthma by inhibiting the expression of HIF-1a,it may improve airway remodeling in asthma by inhibiting the expression of TGF-?1. |
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