经导管局部灌注紫杉醇模拟药物涂层球囊预防小型猪髂总静脉狭窄的实验研究

Experimental study on prevention of common iliac vein stenosis in miniature pigs by regional perfusion of paclitaxel to simulate drug-coated balloons

目的建立小型猪髂总静脉狭窄模型。观察模拟药物涂层球囊(drug-coated balloon,DCB)对髂总静脉狭窄段的影响及安全性评估。方法取20头幼龄、健康、雄性小型猪实施静脉全身麻醉后,以过大球囊损伤小型猪髂总静脉建立动物模型。将建模成功的小型猪随机分为实验组和对照组。实验组以双球囊封堵灌注紫杉醇处理狭窄段静脉,对照组不进行此操作。术前及术后2周抽取静脉血,术前及术后2月静脉造影及观察狭窄段静脉病理切片。比较2组小型猪肝肾功能指标、髂总静脉管腔内径及管壁组织学改变情况。结果 17头小型猪存活至实验终点。实验组(n=9)与对照组(n=8)术后2周谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酐(Cr)及血尿素氮(BUN)相比,差异无显著性(P>0.05);实验组[(3.74±1.24)mm]与对照组[(2.25±1.41)mm]术后2月管腔内径对比,差别有显著性(P<0.05);镜下,实验组与对照组处理段髂总静脉内膜、中膜均增厚,且对照组增厚更明显。结论过大球囊扩张小型猪髂总静脉,制备小型猪髂总静脉狭窄模型可行;经导管局部灌注紫杉醇对小型猪肝肾功能影响不大;模拟DCB可减轻小型猪髂总静脉狭窄程度。

Objective To establish the common iliac vein stenosis model in miniature pigs.Next,to observe the influence and evaluate the safety of simulated drug-coated balloons(DCB)on the stenosis segment of the common iliac vein.Methods Twenty young and healthy male miniature pigs were selected for intravenous general anesthesia.Under anesthesia,the animal model was established by oversized balloon dilatation.After the animal model was successfully established,the miniature pigs were randomly divided into an experimental group and control group.Stenosis segment veins in miniature pigs of the experimental group were occluded by two balloons and perfused with paclitaxel.These steps were not performed in miniature pigs from the control group.Venous blood specimens were taken before and two weeks after operation.Venography was performed and pathological sections of stenotic segment veins observed before and two months after the operation.Hepatorenal function index,diameter of the common iliac vein,and histological changes of the venous wall were compared between both groups.Results Seventeen miniature pigs survived to the end of the experiment.Two weeks after the operation,there were no significant differences(P>0.05)between the experimental group(n=9)and control group(n=8)regarding alanine aminotransferase,aspartate aminotransferase,creatine,and blood urea nitrogen values.However,two months after the operation,lumen diameter was significantly different(P<0.05)between the experimental group[(3.74±1.24)mm]and control group[(2.25±1.41)mm].Compared with the untreated contralateral common iliac vein,the intima and media of the target vein were thicker in both the experimental group and control group.Indeed,this was more obvious in the control group than experimental group.Conclusions The common iliac vein stenosis model can be established in miniature pigs by oversized balloon dilatation.Local perfusion with paclitaxel has little effect on hepatorenal function of miniature pigs.Using this approach,simulated DCB can reduce the degree of common iliac vein stenosis in miniature pigs.