摘要
目的探讨局部应用紫杉醇对兔气管机械损伤后的瘢痕形成发生抑制作用的可能性、安全性及其机制。方法将40只新西兰大耳白兔随机分为4组：阴性对照组，盐水对照组，低浓度治疗组（0．4mg／m1）及高浓度治疗组（1．0mg／m1），4组均行气管切开，阴性对照组气管切开后直接采集气管标本进行组织学检查及免疫组织化学分析；其余3组气管切开后行机械磨损，低浓度治疗组和高浓度治疗组磨损后分别于磨损处局部应用0．4mg／ml的紫杉醇和1．0mg／ml的紫杉醇，作用3min，盐水对照组给予0．9％生理盐水，作用3rain；术后21d采集气管标本，进行组织学、管腔狭窄程度检测和免疫组织化学分析，应用透射电镜观察紫杉醇诱导细胞凋亡的超微结构。结果低浓度治疗组和高浓度治疗组的管腔狭窄率均较盐水对照组明显降低，低浓度治疗组为（27±8）％，高浓度治疗组为（22±7）％，盐水对照组为（59±13）％；病理切片结果显示低浓度治疗组和高浓度治疗组成纤维细胞数量及炎性细胞数量均较盐水对照组明显减少。免疫组织化学结果显示低浓度治疗组和高浓度治疗组的肿瘤坏死因子一B，和血管内皮生长因子阳性细胞表达均较盐水对照组明显减少；透射电镜可见紫杉醇诱导细胞凋亡及细胞器损害的超微结构表现。结论局部应用紫杉醇对兔气管机械损伤后的瘢痕形成有明显的抑制作用，呈剂量依赖性。局部给予紫杉醇在抑制气管瘢痕狭窄方面可能具有潜在的临床价值。
Objective To investigate the effect of local application of paclitaxel on airway scar formation after airway injury in rabbits. Methods 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. Results 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 groupⅠ and group 11 were significantly fewer than in saline control group. The TGF-131 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. Conclusions Local application of paclitaxel inhibits airway scar formation after airway injury in rabbitmodel, 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.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2013年第3期202-206,共5页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
北京市自然科学基金（7102053）
关键词
紫杉醇
气管狭窄
瘢痕组织
免疫组织化学
透射电镜
Paclitaxel
Airway stenosis
Scar tissue
Immunohistochemistry
Transmissionelectron microscope
