| Tuberculous airway stenosis is the most frequently cause of benign airway stenosis in our country,leading to patients with ventilatory dysfunction,loss of lung function,severe respiratory failure,or even suffocation.However,the pathogenesis is still not clear.Airway inflammation plays an important role in airway stenosis.Studies have shown that the incidence of tracheal stenosis or tracheal stenosis after tracheal intubation or tracheostomy is associated with local inflammation and systemic inflammatory response,resulting in the activation of fibroblasts on the damaged trachea,resulting in sustained or excessive proliferation of fibroblasts,leading to airway stenosis.By inhibiting the inflammatory response,down-regulating the expression of inflammatory cytokines and inhibiting the hyperplasia and fibrosis of granulation tissue,we can effectively reduce the tracheal stenosis after tracheal injury in rabbits.Histone deacetylase 2(HDAC2)is an important factor in the regulation of inflammatory response.Studies have shown that anti-inflammatory drugs such as erythromycin can up-regulate the expression of HDAC2 in macrophages and A549 cells and decrease the release of inflammatory cytokines.Therefore,we hypothesize that HDAC2 may be closely related to tuberculous airway stenosis.This study will evaluate the expression of HDAC2 in tuberculous airway stenosis and investigate the response and regulation of HDAC2 on inflammatory factors in tracheal fibroblasts.Three parts followed as:PART?: Inflammatory expression in patients with tuberculous airway stenosisObjective:To evaluate the expression of systemic inflammation in patients with tuberculous airway stenosis.Methods:Sixty preoperative serum samples of tuberculous proliferative airway stenosis group,tuberculous cicatricial airway stenosis group and normal control group were collected from Hunan Chest Hospital.The expressions of TGF-?1,VEGF,IL-6 and IFN-? were evaluated by enzyme linked immunosorbent assay,the differences between the groups were compared.Results:Serum levels of TGF-?1,VEGF,IL-6 and IFN-? in tuberculous proliferative airway stenosis group were significantly higher than those in tuberculous cicatricial airway stenosis group and normal group(P<0.05),There was no significant difference between tuberculous cicatricial airway stenosis group and normal group(P>0.05).Conclusion:The up-regulation of systemic inflammation is associated with the occurrence of tuberculous airway stenosis in the active period.PART?:The expression of HDAC2 in the tuberculous airway stenosisObjective:To evaluate the expression of HDAC2 in the tuberculous airway stenosis.Methods:Twenty specimens of airway granulation tissue,ten specimens of scar bronchus after surgery from patients with tracheobronchial tuberculosis and ten specimens of normal bronchus after surgery were collected in Hunan Chest Hospital.The expression of TGF-?1,VEGF,NF-?B,HDAC2 were evaluated by immunohistochemical method,the differences between the groups were compared,and the correlation of TGF-?1,VEGF or NF-?B with the expression of HDAC2 was comparatively evaluated.The expression of HDAC2 was evaluated by Western blot method also?Results:1.The expression of TGF-?1,VEGF and NF-?B in tuberculous proliferative airway stenosis group were significantly higher than those in tuberculous cicatricial airway stenosis group and normal group(P<0.05),The expression of HDAC2 in tuberculous proliferative airway stenosis group was significantly lower than those in tuberculous cicatricial airway stenosis group and normal group(P<0.05),There was no significant difference between tuberculous cicatricial airway stenosis group and normal group(P>0.05).The expression of TGF-?1,VEGF and NF-?B were negatively correlated with the expression of HDAC2,and the differences were statistically significant(P<0.05).2.Western blot results showed the expression of HDAC2 protein in granulation tissue of tuberculous proliferative airway stenosis group was significantly lower than that of tuberculous cicatricial airway stenosis group and normal group(P<0.05),There was no significant difference between tuberculous cicatricial airway stenosis group and normal group(P> 0.05).Conclusions:The expression of HDAC2 in tuberculous airway stenosis down-regulation,while the expression of inflammatory cytokines up-regulation.It suggested that HDAC2 was associated with the occurrence of tuberculous airway stenosis and could be used as a target for the treatment of tuberculous airway stenosis.PART?:Response and regulation of HDAC2 on inflammatory factors in fibroblastsObjective:To investigate the response and regulation of HDAC2 on inflammatory factors in tracheal fibroblasts.Methods:Human tracheal fibroblasts were cultured in vitro and divided into fibroblast growth medium group(NC group),fibrobalst growth medium with10ng/m L TGF-?1 group(TGF?1 group),fibroblast growth medium with10ng/m L TGF-?1 and 1mg/L erythromycin group(EM1 group),fibroblast growth medium with 10ng/m L TGF-?1 and 10mg/L erythromycin group(EM10group),the expression of IL-8,TNF-? in the cell culture supernatant were evaluated by enzyme linked immunosorbent assay,The expression of HDAC2 protein were evaluated by Western blot.Results:1.The expression of IL-8 and TNF-? in the supernatant of the TGF-?1 group were significantly higher than NC group(P<0.05);The expression of IL-8 and TNF-? in the supernatant of EM1 group and EM10 group were significantly lower than TGF-?1 group(P<0.05).There was no significant difference between the EM1 group and the EM10 group.2.The expression of HDAC2 protein in TGF-?1 group was slightly lower than that in NC group.The expression of HDAC2 protein in EM1 group and EM10 group were higher than that in TGF-?1 group(P<0.05).Conclusions:1.The down-regulation of tracheal fibroblasts HDAC2 stimulated by TGF-?1 attenuates the inhibitory effect on the expression of inflammatory factors.2.The expression of HDAC2 in tracheal fibroblasts was restored and enhanced by erythromycin intervention,which could inhibit the expression of inflammatory factors. |
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