经脾种植VX2瘤株悬液建立兔肝转移瘤模型

Establishment of rabbit liver metastasis model by splenic implantation of VX2 tumor strain suspension

目的探讨经脾种植VX2瘤株构建肝转移瘤(LM)模型的可行性及能否成为LM临床和基础研究的理想动物模型。方法选取40只新西兰大白兔。制备VX2瘤株悬液。经左上腹切口将脾脏牵拉出腹腔,用1mL注射器将瘤株悬液注入脾脏,注射后将脾脏纳入腹腔,逐层缝合。2周后行上腹部增强CT扫描,观察LM模型肝内影像学表现。将兔处死行大体解剖,观察LM在肝内分布。对LM脱水、固定后行苏木精-伊红(HE)染色,观察其镜下表现。结果40只兔VX2肝转移瘤模型成功种植37只,种植成功率为92.5%。1只兔种植中麻醉死亡,1只未种植成功,1只CT增强扫描时死亡。37只兔上腹部增强CT扫描显示肝内转移瘤强化,周边呈环形强化,中心区未见强化,与临床上常见消化道LM增强CT表现一致;大体解剖显示肝内各叶有大小不等多发LM,分布无明显特点,与临床上肿瘤经门静脉途径转移至肝脏的特点一致;镜下见LM中心区为坏死细胞,外周区表现为浓染的肿瘤细胞、炎性细胞等。结论经脾种植VX2瘤株悬液可成功建立兔LM模型,脾脏转移至肝脏的转移瘤更符合临床上消化道肿瘤经门静脉途径转移至肝脏模式。该模型值得在临床和基础研究中推广。

Objective To explore the feasibility of establishing a liver metastasis (LM)model by splenic implantation of VX2 tumor strain,and to discuss whether it can be used as an ideal animal model for clinical and basic research of LM.Methods A total of 40 New Zealand white rabbits were selected for this study.The VX2 tumor strain suspension was prepared.Through left upper abdominal incision the spleen was pulled out of the abdominal cavity,with a 1 mL syringe the tumor strain suspension was injected into the spleen,then,the spleen was pushed back into the abdominal cavity and the abdominal wall was sutured layer by layer.Contrast- enhanced CT scan of the upper abdomen was performed two weeks after the procedure to observe the imaging manifestations of LM lesions.The experimental rabbits were sacrificed for gross anatomy, and the distribution of LM lesions was determined.After dehydration and fixation of LM lesions,hematoxylineosin( HE)staining of tissue slices was made for microscopic examination.Results Successful implantation of VX2 tumor strain suspension was achieved in 37 experimental rabbits,the planting success rate was 92.5%. One rabbit died due to intraoperative anesthesia,implantation of VX2 tumor failed in one rabbit,and one rabbit died during contrast- enhanced CT scan.Contrast- enhanced CT scan of the upper abdomen in 37 rabbits demonstrated that intrahepatic metastatic lesions showed enhancement area with periphery ring - shaped enhancement and no central enhancement was observed,which were consistent with the enhanced CT presentation of LM lesions from commonly- seen digestive tract tumors.Gross anatomy revealed that multiple liver metastases with varying sizes were found in each lobe of liver,and their distribution pattern had no obvious characteristics,which was consistent with the pathological features of hepatic metastases via portal vein approach.Microscopically,there were necrotic cells at the central area of LM lesion and densely- stained tumor cells together with inflammatory cells at the peripheral zone.Conclusion The rabbit LM model can be successfully established by transplanting VX2 tumor strain suspension in spleen,and the LM lesions metastasized from the spleen is quite consistent with the lesions metastasized from upper digestive tract tumor through portal vein.Therefore,this model is worth popularizing in clinical and basic researches.