The Expression And Significance Of HDAC2 In Human Granulation Tissue Of Tracheal Stenosis Caused By Tracheal Intubation And Tracheotomy

Background and Objective:Histone Deacetylases 2(HDAC2)is a very important subtype of the Histone deacetylases(HDACs)family.Studies have shown that HDAC2 is a key factor in regulating the expression of inflammatory genes,and it has been confirmed that it is related to many diseases such as chronic obstructive pulmonary disease of respiratory system and asthma.In animal model experiments,upregulation of HDAC2 protein can reduce the release of inflammatory factors.In cell experiments,upregulation of HDAC2protein inhibited inflammatory response in tracheal mucosal cells and A549cells,and accelerated apoptosis.Inhibit inflammation,can inhibit the excessive animal model of tracheal granulation tissue hyperplasia and fiber formation,promote the healing of tracheal injury wound,effectively alleviate the tracheal stenosis caused by tracheal injury in animal models,the above studies suggest the HDAC2 may participate in the animal model of the onset of benign tracheal stenosis in the process,but currently HDAC2 in the expression and role of benign tracheal stenosis group is unclear.This study by testing after tracheal intubation and tracheotomy HDAC2 expression in granulation tissue in patients with tracheal stenosis,and the detection of peripheral blood serum of transforming growth factor beta 1(TGF beta 1)and vascular endothelial growth factor(VEGF-A),A interleukin 8(IL-8)the expression of cytokines and inflammation factors such as situation,and to explore HDAC2,TGF-β1,VEGF-A,and the expression of IL-8 relates to the occurrence and development of tracheal stenosis.The aim is to provide theoretical basis and new ideas for clinical prevention and treatment of tracheal stenosis after injury.Methods:35 cases were collected from the department of respiratory and critical care medicine of the Second Affiliated Hospital of Guangxi Medical University.According to the causes of tracheal stenosis,there were 20 cases of tracheal intubation stenosis group and 15 cases of tracheal incision stenosis group.Diagnostic criteria:tracheal stenosis in this study has a history of tracheal intubation and tracheostomy,appear different degree of symptoms such as wheezing,difficulty breathing,combining with the above medical history,clinical manifestation,and through bronchoscopy confirm tracheal tube cavity stenosis,CT and X ray film pressure of tracheal stenosis caused by tumor thereof,can be in the diagnosis of the disease.Inclusion criteria:All patients with tracheal stenosis were confirmed by respiratory endoscopy in our hospital;(2)Patients who were recently treated with macrolides,hormones and immunosuppressive or enhancers should stop taking the drugs for at least 7 days.Exclusion criteria:Congenital tracheal stenosis;Tracheal stenosis caused by tracheal tumor or connective tissue disease;Patients with tracheal stenosis caused by tracheal bronchial tuberculosis.Patients treated with macrolides,hormones and immunosuppressive or enhancers within 7 days.The sampling site is the fresh granulation tissue of the narrow site.Preoperative peripheral venous blood 5-10ml was extracted.Normal control group:15 cases of normal airway mucosal tissue.Sample sources of the normal group:patients who were found pulmonary nodules or pulmonary shadows by accident during physical examination in our hospital and who were required to have bronchoscopy biopsy in the department of respiratory and critical disease medicine of our hospital were included in the inclusion criteria:(1)All vital signs were normal before fiberoptic bronchoscopy;leukocytes in blood routine were between4.0-10.0×10~9/L;and inflammatory indicators such as CRP were all within the normal range;(2)All patients were treated with bronchoscopy.(2)Fiberoptic bronchoscopy confirmed that the appearance of trachea was normal,without endotracheal stenosis,inflammation,infection and purulent secretion attachment.All subjects obtained their consent and signed informed consent,and a small amount of normal tracheal mucosal tissue was forceps during biopsy for experimental study.5-10ml of peripheral venous blood was extracted before fiberoptic bronchoscopy.Exclusion criteria:Patients with active tuberculosis and pulmonary infection were excluded according to the pathological results of lung lesion biopsy.Serum levels of transforming growth factor 1(TGF-1),vascular endothelial growth factor A(VEGF-A)and inflammatory factor IL-8were measured by ELISA.Western Blot was used to determine the expression level of HDAC2 protein in tracheal mucosa and granulation tissue.Results:Western Blot test results:postoperative stenosis group and endotracheal intubation after tracheotomy narrow set of granulation tissue,respectively,compared with normal control group,the expression of HDAC2protein are cut,are statistically significant differences(all P<0.05),postoperative stricture endotracheal intubation group and tracheotomy after comparison between groups,narrow stenosis group than endotracheal intubation after tracheotomy HDAC2 protein expression of postoperative stenosis group cut more apparent,but there was no statistically significant difference between the two(P>0.05).ELISA results:Compared with the normal control group,the stenosis group after endotracheal intubation and tracheotomy showed higher concentrations of TGF-1,VEGF-A and inflammatory factor IL-8 in peripheral blood serum,with statistically significant differences(all P<0.05).There was no significant difference between the stenosis group after endotracheal intubation and the stenosis group after endotracheal resection(P>0.05).Conclusions:The expression of HDAC2 protein in the granulation tissue with abnormal hyperplasia in the stenosis site of trachea was lower in both the stenosis group after tracheal intubation and the stenosis group after tracheotomy than in the normal group,suggesting that HDAC2 may be related to the occurrence and development of stenosis after tracheal injury.The expression level of transforming growth factor 1(TGF-1)vascular endothelial growth factor A(VEGF-A)inflammatory factor IL-8 in peripheral blood of patients with tracheal stenosis after endotracheal intubation and tracheotomy was higher than that of the normal control group,which may indicate the progression of tracheal stenosis.