迷迭香酸钠抗小鼠H22肝癌细胞移植瘤淋巴结转移的研究

摘要

Objective: To investigate the effect and molecular mechanism of Sodium Rosmarinate (SR) on lymph node metastasis of hepatocarcinoma in vivo. Methods: H22 cells were subcutaneously injected into paws of male Kunming mice to establish a HCC lymph node metastasis model. Mice were randomly divided into seven groups: normal, model, 5 mg/kg Adriamycin (ADM), 40 mg/kg Resveratrol (RSV), 50 mg/kg Sodium Rosmarinate (50 mg/kg SR), 100 mg/kg Sodium Rosmarinate (100 mg/kg SR) and 200 mg/kg Sodium Rosmarinate (200 mg/kg SR). Five days after the injection, the mice began to receive drug treatment via intraperitoneally injection for 21 days. On the 30 th day, mice were sacrificed. The xenografts, lymph nodes and immune organs were observed, HE staining was used to detect the metastasis of H22 cells in lymph node, Realtime-PCR were subject to measure expressions of metastasis related factors (MMP-9, VEGF-C). Results: SR can inhibit the proliferation of tumor cells, reduce the lymph node metastasis of HCC, and have no irritation to immune organs; it can also significantly inhibit expressions of lymphangiogenesis related factors (MMP-9, VEGF-C). Conclusion: It has been demonstrated that SR has significant anti-metastasis effects against HCC via down-regulating expressions of MMP-9 and VEGF-C, SR may be a promising new drug for HCC with its low toxicity and anti-metastasis activity.%目的:探讨迷迭香酸钠对H22肝癌细胞小鼠移植瘤淋巴结转移的药理作用及相关机制.方法:小鼠爪垫皮下接种H22细胞, 建立小鼠肿瘤淋巴结转移模型.荷瘤小鼠随机分为:正常对照组、模型组、阿霉素组 (5mg/kg) 、白藜芦醇组 (40mg/kg) 、迷迭香酸钠高 (200mg/kg) 、中 (100mg/kg) 、低 (50mg/kg) 剂量组.造模第5天开始, 各组小鼠每天腹腔注射相应剂量药物, 连续给药21天, 建模第30天后处死小鼠;观测小鼠移植瘤、淋巴结、免疫器官的变化;通过HE染色和Realtime-PCR等技术检测肿瘤淋巴结转移情况以及转移相关因子MMP-9、VEGF-C的表达, 探索迷迭香酸钠对肿瘤淋巴结转移影响.结果:迷迭香酸钠50mg/kg以上剂量能明显抑制肿瘤增殖, 减少其向腘窝、腹股沟淋巴结转移;对小鼠的免疫器官无明显的刺激作用;迷迭香酸钠还可降低肿瘤组织中淋巴管生成因子MMP-9、VEGF-C表达.结论:迷迭香酸钠能通过下调MMP-9、VEGF-C表达而在H22荷瘤小鼠体内发挥显著的抗肝癌淋巴结转移作用, 其展现出低毒优点, 具有良好抗肝癌转移活性.