The pilot study of the effect of paclitaxel by local application on scar formation after airway injury in rabbits

Abstract

To investigate the effect of local application of paclitaxel on airway scar formation after airway injury in rabbits. Forty New Zealand rabbits were randomly divided into four groups, negative control group (n = 10), saline control group (n = 10), group I (n = 10), group II (n = 10). All rabbits received tracheotomy. In negative control group, the specimens were harvested for histological examination and immunohistochemical analysis immediately after tracheotomy;in other three groups, rabbits received airway injury after tracheotomy. In group I and group II, 0.4 mg/ml and 1.0 mg/ml paclitaxel was applied locally in injured airway segment for 3 minutes after airway injury. The normal saline was used in control group for 3 minutes. The animals were killed in 21 days after operation. The specimens were harvested for histological examination and immunohistochemical analysis. Transmission electron microscopy was employed to observe the ultrastructure of paclitaxel-induced apoptotic cells. The degree of stenosis in group I and group II were significantly decreased compared to those in saline control group [saline control group (59 ± 13)%, group I (27 ± 8)%, group II (22 ± 7)%]. Histological examination showed fibroblast cells and inflammatory cells in group I and group II were significantly fewer than in saline control group. The TGF-β1 positive cells and VEGF positive cells in group I and group II were significantly decreased compared to those in saline control group (P < 0.05). Paclitaxel-induced cell apoptosis and injured cell organs were observed by transmission electron microscopy. Local application of paclitaxel inhibits airway scar formation after airway injury in rabbit model, and the inhibition is dose dependent. Paclitaxel may have a therapeutic potential for the treatment of airway stenosis caused by endotracheal intubation, tracheotomy or implantation of airway stents.