背景与目的:以细胞膜电穿孔效应为核心的电化学治疗已开展二十余年.其主要机理为脉冲电场的膜穿孔促进外源药物、抗体或基因向胞内弥散。本课题组的的期研究已证实高能陡脉冲电场能使肿瘤细胞膜发生不可逆性电穿孔,从而导致肿瘤细胞的直接死亡。本实验主要观察陡脉冲电场对兔VX2乳腺移机瘤毛细淋巴管的影响。方法:成功建立VX2兔移植性乳腺瘤模型,采用美蓝灌注、酶组织化学5-核苷酸碱性磷酸酶(5'-AMP—ALPase)双重染色法、电镜技术观察陡脉冲处理后瘤体局部毛细淋巴管的形态学变化.结果:经美蓝灌注显示.陡脉冲处理后的癌组织边缘模糊,无线样或环状的淋巴管;双重染色显示,靶区内未见任何呈阳性染色的淋巴管。瘤体边缘仅见毛细淋巴管碎片样结构:透射电镜下见毛细淋巴管的完整性和连续性均被破坏。结论:陡脉冲电场破坏了靶区癌组织边缘的毛细淋巴管,因此可减少治疗后局部癌细胞淋巴转移的可能性。
BACKGROUND & OBJECTIVE: Electrochemotherapy mediated by electric pulse has become a multidisciplinary biomedical engineering technique in modern medical science. Its main mechanisms are enhancing the diffusion of chemotherapeutic drugs, antibodies, or genes into the inner part of tumor cells mediated by membrane-electropermeabilization caused by electric pulse. Our previous studies confirmed that steep pulsed electric field (SPEF) could irreversibly cause membrane electropermeabilization, and lead to death of tumor cells. This study was to explore the acute killing effects of SPEF on lymphatic capillaries in VX2 implanted breast cancer in rabbits. METHODS: Tumor model of VX2 implanted breast cancer was successfully established in rabbits. Isosulfan blue staining, 5' -AMP-ALPase enzymohistochemical double staining, and electron microscopy was used to observe the morphologic changes of local lymphatic capillaries around cancer tissues exposed to SPEF. RESULTS: After exposed to SPEF, no lymphatic vessels were found with isosulfan blue staining, only blurred structures were observed; enzymohistochemistry showed no positively stained lymphatic vessels, only fragmental structures around cancer tissues were observed; integrity and continuity of lymphatic endothelium were destroyed under transmission electron microscope. CONCLUSION: SPEF has the potential to destroy lymphatic capillaries around VX2 implanted breast cancer, and can decrease the possibility of post-treatment lymphatic metastasis.