管腔外局部应用紫杉醇对豚鼠胆管对端吻合术后吻合口愈合的作用

Effect of Local Delivery of Paclitaxel on Anastomotic Wound Healing of the Common Bile Duct in Guinea Pig

目的探讨局部应用紫杉醇对豚鼠动物模型胆管对端吻合术后瘢痕愈合、狭窄发生抑制作用的可能性。方法制作豚鼠胆管对端吻合动物模型。将42只豚鼠按术后时间(3d、2周、1个月)随机分为3组,每组按紫杉醇组与对照组各分为2组,每组7只。紫杉醇组于显微吻合操作完成后吻合口管壁外局部涂抹紫杉醇溶液(1000μmol/L,0.05ml),作用10min左右。术后分别于3d、2周、1个月时取材,与对照组比较,进行组织学、管壁厚度检测。应用透射电镜观察紫杉醇诱导细胞凋亡的超微结构。结果术后胆管壁呈炎症反应,内膜增生显著。术后3天和1个月时,紫杉醇组管壁厚度均小于对照组[3天:(574.41±24.53)μmvs(802.98±24.42)μm,t=-6.604,P=0.000;1个月:(1383.36±36.64)μmvs(1518.56±34.89)μm,t=-2.672,P=0.020)]。透射电镜可见紫杉醇诱导细胞凋亡及细胞器损害超微结构表现。结论管腔外局部单次使用紫杉醇1个月内可起到延缓豚鼠动物模型胆管管壁增厚的作用。

Objective To investigate the effect of local delivery of paclitaxel on bile duct scar formation and biliary stricture in guinea pig.Methods Models of end-to-end anastomosis of the common bile duct were established in 42 guinea pigs.The animals were randomly divided into paclitaxel and control groups.In the paclitaxel group,the drug solution（1000 μmol/L,0.05 ml） was smeared onto the anastomotic wound before closing the abdomen.The animals were killed in 3 days,2 weeks,and 1 month after the operation（7 in each group at each time point）.The sepcimens of the common bile duct were obtained for histological examination.Transmission electron microscopy was employed to observe the ultrastructure of paclitaxel-induced apoptotic cells.Results Histological examination showed inflammatory reaction and hyperplasia of the bile duct wall.The bile duct wall of the paclitaxel group was significantly thiner than that of the control group in 3 days and 1 month after the operation [3 days：（574.41±24.53）μm vs（802.98±24.42）μm,t=-6.604,P=0.000;1 month：（1383.36±36.64） μm vs（1518.56±34.89）μm,t=-2.672,P=0.020].Paclitaxel-induced cell apoptosis and injured cell organs were found by transmission electron microscopy.Conclusion Single local delivery of paclitaxel can inhibit biliary stricture in one month.