糖尿病裸鼠胰腺癌神经浸润模型建立及其评价

Establishment and evaluation of in vivo model of sciatic neural invasion by PanCa cells in diabetic nude mice

目的诱导裸鼠糖尿病模型,构建糖尿病裸鼠坐骨神经肿瘤浸润模型,观察高血糖对胰腺癌神经浸润的影响。方法 12只3-5周龄裸小鼠分成高糖组和血糖正常组,两组右下肢坐骨神经内注射胰腺癌细胞BXPC-3构建坐骨神经神经浸润模型,左下肢作为对照。每周观察后肢粗略行为、坐骨神经指数和肌力变化,判定坐骨神经功能变化;6周后处死裸鼠,通过HE染色、免疫组化等方法观察各组神经浸润发生的情况。结果高糖组接种1周即出现坐骨神经功能障碍,5周4/6出现完全瘫痪;血糖正常组2周开始出现坐骨神经功能障碍,5周1/6出现完全瘫痪;糖尿病组右侧肢体两趾之间距离在观察过程中逐渐下降,到第6周时已经明显下降,与注射后第1周比,有明显统计学差异(P<0.05)。高糖组肿瘤直径较正常血糖组增大(P<0.05);HE染色和免疫组化显示,两组肿瘤的生长并非单纯的压迫性生长,而是侵入神经内进行生长。结论糖尿病裸鼠胰腺癌神经浸润模型是一种成熟的动物模型,可用于研究糖尿病在体内如何促使神经浸润的进展。

Objective To establish the in vivo model of sciatic neural invasion by PanCa cells in diabetic nude mice for exploring the effects of hyperglycemia on the sciatic neural invasion in pancreatic cancer.Methods The 3-5-week-old male athymic nu/nu mice were randomized into diabetic group and normal glucose group.The streptozotocin and normal saline were intravenously administrated to establish the diabetic model in two groups,respectively.BXPC-3 was injected via the sciatic nerve of the right hind limb to induce sciatic nerve paralysis in nude mice with the left limb as the controls.The sciatic nerve function was measured weekly by monitoring the gross behavior,limb function,and sciatic nerve index.All mice were euthanized six weeks after tumor cells injection,and the sciatic nerve and the tumor were excised for histopathological analysis.Results Mice began to develop the right hind limb dysfunction one week after injecting the cancer cells in diabetic group and 2 weeks after injection in normal glucose group.And 4/6 of mice developed the complete paralysis five weeks after tumor implantation in diabetic group,and only 1/6 in normal glucose group.The right paw span decreased more significantly in diabetic group than that in normal group six weeks after tumor injection（P〈0.05）.Tumor diameter at the injection site was larger significantly in diabetic group than that in normal group（P〈0.05）.HE and immunohistochemical staining showed that the cancer tissue penetrated the nerve tissue in an invasive manner and did not simply compress the nerve tissue. Conclusion The in vivo model of sciatic neural invasion by PanCa cells in diabetic nude mice is a feasible method and could be used in the study how hyperglycemia promotes the perineural invasion in pancreatic cancer.