长春瑞滨诱导化疗性静脉炎大鼠模型的构建和评价

Construction and evaluation of a chemotherapeutic phlebitis rat model induced by vinorelbine via the dorsalis pedis vein

目的构建一种经大鼠足背静脉注射长春瑞滨注射液诱导的化疗性静脉炎动物模型及评价体系。方法大鼠随机分为空白组和4个不同浓度长春瑞滨模型组,经后肢足背静脉注射0.1 mL生理盐水设为空白组,其余大鼠则分别注射等体积的2、3、4和5 mg/mL长春瑞滨溶液,每日测量患肢体积并计算肿胀率,连续7 d,末次处死动物取病灶足背静脉组织,采用苏木精-伊红(HE)染色法观察组织学改变,同时扫描电镜观察内膜表面微观结构变化。结果经足背静脉注射2、3、4、5 mg/mL长春瑞滨溶液可明显诱发大鼠后肢肿胀,且肿胀率随浓度递增而加剧,同时各浓度组均在第3天达峰值;第7天静脉炎分级显示2 mg/mL组50%大鼠成模,3 mg/mL组为83.3%,而4 mg/mL组和5 mg/mL组大鼠100%造模成功,其中4 mg/mL组Ⅲ级为66.6%,5 mg/mL组Ⅳ级占83.3%;HE染色可见静脉周围组织随长春瑞滨溶液浓度增加呈现炎性细胞浸润、管壁增厚、管腔狭窄及血栓,扫描电镜也显示静脉内皮细胞紧密连接破坏,内膜表面粗糙且粘附血细胞。结论经大鼠足背静脉注射0.1 mL的3~5 mg/mL长春瑞滨溶液可见局部红、肿及条索状静脉,甚至皮肤溃烂,静脉周围组织炎性细胞浸润,静脉壁增厚、管腔狭窄及血栓形成,静脉内膜表面粗糙且粘附血细胞,基本符合临床化疗性静脉炎特征。

Objective To establish and evaluate chemotherapeutic phlebitis model rats induced by vinorelbine via the dorsalis pedis vein.Methods Rats were divided randomly into control and 4 different concentration of vinorelbineinduced model groups.Control rats were injected with 0.1 mL normal saline via the dorsalis pedis vein of the hind limb,while other rats were injected with different concentrations of vinorelbine(2,3,4,5 mg/mL),as above.General observations were performed and the hind limb volume was measured daily for 7 consecutive days to calculate the swelling rate.The rats were then killed and histological changes in the dorsalis pedis vein were observed by hematoxylin and eosin staining.Microstructural changes on the surface of the vascular endometrium were observed by scanning electron microscopy.Results Injection of 2,3,4,5 mg/mL vinorelbine via the dorsalis pedis vein significantly induced hind limb swelling in a concentration-dependent manner,peaking on day 3 in each group.The phlebitis rates on day 7 were 50%in the 2 mg/mL group and 83.3%in the 3 mg/mL group.Phlebitis was also induced in the 4 mg/mL and 5 mg/mL groups,including gradeⅢin 66.6%and gradeⅣin 83.3%.Histopathology showed inflammatory cell infiltration,wall thickening,lumen stenosis,and thrombosis in the tissues surrounding the veins.Scanning electron microscopy showed destruction of tight junctions of venous endothelial cells,and a rough surface of the vascular lining,resultsing in blood cell adhesion.Conclusions Injection of 0.1 mL of 3~5 mg/mL vinorelbine via the dorsalis pedis vein could induce red,swollen,and cord-like veins,as well as infiltration of inflammatory cells around the vein,thickened vein walls,lumen stenosis,and thrombosis.In addition,the surface of the venous intima was rough and adhered to numerous blood cells.All these features are consistent with those of clinical chemotherapeutic phlebitis in terms of the symptoms and pathological structure.