Objective      To determine the effect of transfection of lentivirus vectors carrying tumor necrosis factor receptor associated death domain (TRADD) gene in the canine mucosa of benign esophageal stricture esophageal stents coated with TRADD gene-expressing lentivirus viruses on esophageal stricture after implanting.       Methods      Fifteen experimental dogs were evenly divided into experimental

control

and blank groups (n=5). Benign esophageal stricture models were constructed using argon plasma coagulation (APC). Covered esophageal stents coated with GFP-TRADD gene-expressing lentivirus vector

esophageal stents coated with green fluorescence protein (GFP)-expressing lentiviruses

and regular covered esophageal stents were placed into the dogs from the 3 groups respectively

and the conditions of stent loss were observed after 1 week. Stents were removed

and the degrees of stricture were observed using gastroscopy in 2

3

and 4 weeks after implantation. Experimental dogs were sacrificed after 4 weeks

and Masson Trichrome staining and immunofluorescence assay were performed on esophageal stricture tissues for pathological changes. Western blotting was performed to detect the protein expression levels of TRADD

collagenⅠ

collagenⅢ

and α-smooth muscle actin (α-SMA) in esophageal tissues in the 3 groups.       Results      In 1 week after esophageal stent placement

gastroscopy results showed that all covered stents in the dogs had migrated into the stomach in the experimental group

while the covered stents migrated into the stomach in only 2 and 3 dogs in the control and blank groups

respectively

and those non-migrated esophageal stents were removed by gastroscopy. After removal

the diameters of esophageal stricture sites were measured every week. Significant esophageal stricture occurred again in the dogs of the control and blank groups

while the re-stricture in the experimental group was much milder (P0.01) by repeated measures designed multivariate analysis. Hematoxylin and eosin (HE) staining indicated that the hyperplasia of granulation tissues and fibrous tissues was found in the esophageal stricture tissues of the blank and control groups

while no such obvious changes were seen in the experimental group. Masson Trichrome staining revealed that there were significantly less collagen fibers in the experimental group than the blank group and control group (P0.01). Immunofluorescence assay displayed that GFP was expressed in the submucosal tissues

indicating that TRADD gene-expressing lentiviruses grew in the esophageal submucosa. Western blotting showed that the GFP-TRADD-Flag protein was detected in the experimental group

while the protein was not detected in the blank and control groups

indicating that TRADD gene-expressing lentiviruses were successfully transfected into esophageal submucosal tissues. Western blot results showed that the expression levels of collagenⅠ

collagenⅢ

and α-SMA protein were significantly lower in the experimental group than those in the other 2 groups (P0.05).       Conclusion      Using stents as carriers results in successful transfer of TRADD-expressing lentiviruses into esophageal mucosal tissues

which can inhibit tissue hyperplasia at stricture sites and decrease re-stricture of esophageal stricture sites.