ObjectiveTo investigate the expression of histone deacetylase 2 (HDAC2) in animal model of benign tracheal stenosis, and explore the mechanism of HDAC2 in development of tracheal stenosis.MethodsEighteen rabbits were randomly divided into a blank control group, a model group, and an erythromycin group, with 6 rats in each group. The model group and the erythromycin group underwent tracheostomy, the inner wall of trachea was brushed back and forth with a nylon brush for more than 20 times to induce benign tracheal stenosis. From 7 days before surgery to 9 days after surgery, the model group received gavage with saline, the erythromycin group received gavage with low-dose erythromycin in dose of 15 mg·kg–1·d–1, and the control group did not receive any treatment. On the 10th day after operation, all the rabbits were sacrificed and the trachea was cut to measure the tracheal stenosis. RNA and protein were extracted from the granulation tissue in the stenosis and the relative mRNA expressions of HDAC2, interleukin (IL)-6 and IL-8 in the granulation tissue were detected by real-time fluorescence quantitative PCR. The relative expression of HDAC2 protein was detected by Western blot.ResultsCompared with the blank control group, the tracheal stenosis in the model group was more obvious [(84.60±1.14)% vs.(27.00±6.44)%], the mRNA and protein expressions of HDAC2 were decreased (0.29±0.07 vs. 1.00±0.00, 0.20±0.02 vs. 0.49±0.04), the mRNA expressions of IL-6 and IL-8 were up-regulated (4.22±0.67 vs. 1.00±0.00, 162.72±23.23 vs.1.00±0.00). Compared with the model group, tracheal stenosis in the erythromycin group was relieved [(64.00±12.25)% vs. (84.60±1.14)%], the mRNA and protein expressions of HDAC2 were increased (0.42±0.14 vs. 0.29±0.07, 0.43±0.01 vs. 0.20±0.02), the mRNA expressions of IL-6 and IL-8 were decreased (0.72±0.24 vs. 4.22±0.67, 130.22±7.93 vs. 162.72±23.23). All the differences were statistically significant (all P<0.05). The Pearson correlation coefficient between tracheal stenosis and HDAC2 mRNA relative expression was –0.96 (P<0.05).ConclusionsThe down-regulation of HDAC2 expression in model of benign tracheal stenosis is related to the occurrence and development of tracheal stenosis. The low dose of erythromycin may be used to treat benign tracheal stenosis by up-regulating expression of HDAC2 and thus inhibiting the inflammatory disorder during tracheal injury repair.
Congenital tracheal stenosis (CTS) is a rare but potentially life-threatening disease which results in congnital airway lesion. CTS is often associated with cardiovascular anomalies and presented with a wide spectrum of symptoms. CTS has challenged pediatric surgeons for decades. Various classic approaches and new techniques, including computational fluid dynamics, tissue-engineering trachea, and 3D printing have been proposed for diagnosis and treatment of CTS. This review provides a snapshot of the main progress of diagnosis and treatment of CTS.
ObjectiveTo investigate that the TGF- beta/Smad signaling pathway mediated epithelial mesenchymal transition (EMT) in trachea stenosis after transplantation. Methods180-220 g male rats (n=50) were randomly divided into a control group and an experimental group. no surgical operation rats were in the control group. tracheal transplantation rats (Wistar-SD rat) were in the experimental group. Graft specimens were obtained in rats on 3,7,10,14,35,90 days after operation. HE staining is used to explain the fibrosis degree of tracheal stenosis. The fibrosis degree of tracheal stenosis was detected by calculating the fibrosis rate. Immunohistochemical staining was used to detect transplanted tracheal, such as EMT related molecules E-cadherin, vimentin, alpha-SMA expression, p-Smad2/3 expression and transcription factor ZEB1, Snail1 expression in tracheal graft specimens. ResultsHE staining showed that the tracheal fibrosis rate of the control group was 0.171±0.020, fibrosis rate was 0.537±0.013 (P < 0.01) on the third day after transplantation. The result of immunohistochemical staining showed that vimentin positive epithelial cells increased significantly (P < 0.05). E-cadherin expression significantly reduced (P < 0.05). Compared with the control group, TGF- beta expression increased (P < 0.05) in the experiment group. Compared with the control group, the expression of p-Smad2/3, the transcription factor ZEB1 and Snail1 significantly increased (P < 0.05) in the experiment group. ConclusionMechanism of tracheal stenosis may be due to EMT. At the same time, TGF- beta/Smad signaling pathway and transcription factor ZEB1, Snail1 may regulate the EMT.
Objective To explore the feasibility and safety of extracorporeal membrane oxygenation (ECMO) to support the airway reconstruction for the patients with airway obstruction or stenosis who cannot be ventilated routinely. Methods There were 3 patients received trachea reconstruction procedures assisted by ECMO. Among the patients, 2 cases with tracheal neoplasms underwent fibrobrochoscopy treatments, another one with endotracheal stenosis and fistula received tracheoplasty and semi-tracheostomy. Results ECMO can provide enough oxygenation for the patients with airway obstruction or stenosis and more time for advanced therapies. All three patients recovered after interventional surgeries, in whom one case died due to multiple organ failure caused by esophageal carcinoma metastasis after 3 months, and the others survived with dyspnea classification of 2-3 grade. Conclusion ECMO can be a safe and effective approch for the patients who cannot be ventilated conventionally in airway reconstruction.
Objective To assess the application value of 3-dimensional(3D) printing technology in surgical treatment for congenital tracheal stenosis. Methods We retrospectively analyzed the clinical data of preoperative diagnosis, intra-operative decision-making and postoperative follow-up of four children with congenital tracheal stenosis under the guidance of 3D printing in our hospital between February 2013 and May 2014. There were 3 males and 1 female aged 23.0±7.1 months. Among them, two children were with pulmonary artery sling, one with ventricular septal defect, and the other one with tetralogy of Fallot. The airway stenosis was diagnosed preoperatively by chest CT scan and 3D printing tracheal models, and was confirmed by the help of bronchoscopy under anesthesia. During operation the associated cardiac malformation was corrected firstly under extracorporeal circulation followed by tracheal malformation remedy. The design and implementation of tracheal operation plans were guided by the shape and data from 3D printing trachea models. There were two patients with long segment of tracheal stenosis who received slide anastomosis. And the other two patients were characterized with tracheal bronchus, one of which combined ostial stenosis of right bronchial performed extensive slide anastomosis, and the other one performed end to end anastomosis. Results All the children’s preoperative 3D printing trachea models were in accord with bronchoscopy and intra-operative exploration results. Intra-operative bronchoscopy confirmed that all tracheal stenosis cured completely. All anastomotic stomas were of integrity, and all the luminals were fluent. There was no operative death or no serious complication. During 1-2 years follow-up, all patients breathed smoothly and their airways were of patency by postoperative 3D printing trachea model. Conclusion 3D printing can provide a good help to congenital tracheal stenosis in preoperative diagnosis, the design of operation plan, intra-operative decision-making and manipulation, which can improve the operation successful rate of tracheal stenosis.
ObjectiveTo establish a simple and stable model of benign tracheal stenosis in SD rats by nylon brush scraping induced mechanical injury, and to observe the pathological changes of tracheal tissue at different time points after modeling.MethodsTwenty SD rats were divided into sham operation group (10 rats) and stenosis model group (10 rats) by random number method. Symptoms and survival conditions were observed, tracheal tissues were obtained, granulation tissue proliferation was observed, and stenosis indexes were measured and compared. Another fifteen rats were sacrificed at different time points (days 0, 2, 4, 6, and 8) after modeling. Tracheal tissues were obtained, HE staining and Masson staining were performed to observe pathological changes with time.ResultsThe survival rate of the sham operation group was 100% on the 8th day after operation, and the survival rate was 0% on the 8th day after operation in the stenosis model group. The difference in survival condition between the two groups was statistically significant (P=0.000 1) by Log-rank test. The stenosis index in the sham operation group was (6.12±1.78)%, and in the stenosis model group was (60.28±12.56)%. The difference in the stenosis between the two groups was statistically significant (P<0.000 01). HE staining results showed that the tracheal lumen was unobstructed and no granulation tissue hyperplasia or stenosis was found in the sham operation group. The epithelial mucosa was intact and smooth, and the cilia structure was clearly visible. It was a pseudo-stratified ciliated columnar epithelium, which was consistent with the characteristics of normal airway mucosa. While in stenosis model group, the lumen was significantly narrowed, and the stenosis was mainly caused by granulation tissue hyperplasia. No epithelial structure was observed, or epithelial structure was extremely abnormal. Masson staining showed that the fibroblasts in the injured site increased first and then decreased, and the collagenous fiber (blue) in the injured site gradually increased with time.ConclusionsA model of benign tracheal stenosis in rats can be successfully established by nylon brush scraping induced mechanical injury. The modeling method is simple, controllable and reproducible. The model can be widely used in the investigation of pathogenic mechanism for benign airway stenosis and efficacy exploration of new treatment.