靶向微泡介导干预淋巴引流及淋巴管新生抑制乳腺癌淋巴转移的研究

淋巴系统的免疫平衡在乳腺癌免疫监视与维持体液的动态平衡中发挥积极作用。肿瘤的发生、进展及淋巴转移各个阶段伴随着和淋巴液引流不畅和淋巴管新生的病理生理改变，在肿瘤进展不同阶段互为因果导致机体免疫系统的代偿功能向免疫沉默转变，机体抗肿瘤免疫能力下降。本项目拟以小鼠乳腺癌为模型，经肿瘤周边皮下注射VEGF3siRNA靶向微泡用以抑制淋巴管新生；同时在微泡介导下淋巴管内置管负压引流淋巴液用以恢复淋巴系统抗肿瘤免疫功能。其次，通过监测VEGFR-C等表达变化及新生淋巴管密度变化验证淋巴管新生抑制效果；基于监测淋巴液补体C3等指标验证干预淋后免疫的改善。最终，课题结合肿瘤大小及淋巴结大小和形态的变化，利用复合微泡结合人工负压吸引淋巴液的方法、改善淋巴引流、抑制淋巴管过度新生、恢复机体抗肿瘤免疫能力，探索抵御乳腺癌淋巴转移的新机制。课题研究对于探索早期抑制乳腺癌淋巴转移的新方法有积极意义。

The immune balance of the lymphatic system plays an active role in breast cancer immune surveillance and maintaining the homeostasis of body fluids. Tumor development, progression and lymphatic metastasis are accompanied by poor lymphatic drainage and pathophysiological changes of lymphatic neovascularization. Mutual causal effects at different stages of tumor progression lead to the compensation function of the body's immune system to immune silencing, and the body's anti-tumor immunity declines. This project intends to use mouse breast cancer as a model, and subcutaneous injection of VEGF3 siRNA targeting microbubbles to inhibit lymphangiogenesis; and microbubble-mediated lymphatic drainage in the lymphatic channel to restore lymphatic anti-tumor immunity function. Secondly, the lymphangiogenesis inhibition effect was verified by monitoring the expression changes of VEGFR-C/D and the changes of lymphatic channel density. Meanwhile ,based on the changing in lymphatic fluid by C3 is for verify the improvement of anti-tumor immunity after lymphatic drainage intervention. Finally, the subject combines tumor size and lymph node size and morphology changes, using composite microbubbles combined with artificial negative pressure to attract lymph fluid, improve lymphatic drainage, inhibit lymphatic hyperplasia, restore the body's anti-tumor immunity, is to explore a new mechanism for transfer of the defense against breast cancer lymph a new mechanism for transfer. The research of the subject has positive significance for exploring new methods for inhibiting lymphatic metastasis of breast cancer in the early stage.