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目的:观察肺岩宁颗粒对Lewis肺癌小鼠肿瘤相关巨噬细胞的影响及肿瘤肺转移的抑制作用。方法:取Lewis肺癌细胞接种在C57BL/6小鼠右腋皮下,制备Lewis肺癌荷瘤鼠模型。C57BL/6小鼠随机分为正常组、模型组、顺铂组、肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组,除正常组外均造模。予相应干预(中药或生理盐水灌胃,顺铂腹腔注射),14 d后观察小鼠生存质量、肺转移灶及计算肺转移抑制率;ELISA法检测血清中细胞因子IL-10、IL-12、转化生长因子(TGF)-β1含量;免疫组织化学染色检测肿瘤组织中肿瘤相关巨噬细胞CD206的表达;Western blot法检测肿瘤组织中基质金属蛋白酶(MMP)-2、MMP-9、核转录因子(NF)-κBp65的表达。结果:模型组、顺铂组小鼠生存质量最差,肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组小鼠生存质量较好。肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组3组的肺转移抑制率均明显高于顺铂组。模型组IL-10含量明显高于正常组,各治疗组IL-10含量均显著低于模型组(P<0.05);与顺铂组比较,肺岩宁方组、肺岩宁颗粒组IL-10含量均明显升高(P<0.05)。肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组IL-12含量均显著高于模型组及顺铂组(P<0.05)。与顺铂组比较,肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组TGF-β1均显著降低(P<0.05)。肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组均可抑制CD206的表达(M2型),但顺铂组和肺岩宁颗粒联合顺铂组抑制更为明显。肺岩宁方组、肺岩宁颗粒组、肺岩宁颗粒联合顺铂组肿瘤组织中MMP-2、MMP-9、NF-κBp65的表达明显低于顺铂组(P<0.05)。结论:肺岩宁颗粒能明显改善小鼠生存质量及抑制肿瘤转移,其机制可能是干预NF-κB信号通路并进一步调节肿瘤相关巨噬细胞。
Objective: To observe the effect of Feiyanning granule on tumor-associated macrophages in mice with Lewis lung cancer and its inhibitory effect on lung metastasis. Methods: Lewis lung carcinoma cells were inoculated subcutaneously into the right axilla of C57BL / 6 mice to prepare Lewis lung carcinoma bearing mice model. C57BL / 6 mice were randomly divided into normal group, model group, cisplatin group, Feiyanningfang group, Feiyanning granule group, Feiyanning granule combined with cisplatin group, except the normal group. After 14 d, the quality of life, lung metastasis and the inhibition rate of lung metastasis were observed. Serum IL-10, IL-12 levels were measured by ELISA , And the content of transforming growth factor (TGF) -β1. The expression of CD206 in tumor-associated macrophages was detected by immunohistochemical staining. The expressions of matrix metalloproteinase-2, MMP-9 and nuclear transcription Factor (NF) -κBp65 expression. Results: The mice in model group and cisplatin group had the poorest quality of life, and the quality of life in the mice in the Feiyanfang group, the Feiyanning granules group, the Feiyanning granules group and the Cisplatin group was better. The inhibitory rates of lung metastasis in three groups of Feiyanningfang, Feiyanning granule, Feiyanning granule combined with cisplatin were significantly higher than that of cisplatin group. The content of IL-10 in the model group was significantly higher than that in the normal group, and the content of IL-10 in each treatment group was significantly lower than that in the model group (P <0.05). Compared with cisplatin group, IL- 10 content were significantly increased (P <0.05). The content of IL-12 in Feiyanning group, Feiyanning granules group, Feiyanning granules combined with cisplatin group were significantly higher than those in model group and cisplatin group (P <0.05). Compared with the cisplatin group, TGF-β1 in the lungs of Ningfang, Feiyan Granulation, Feiyanning Granules and Cisplatin were significantly decreased (P <0.05). The expression of CD206 (type M2) was inhibited in the Feiyanning group, Feiyanning granule group, Feiyanning granule combined with cisplatin group, but the inhibition was more obvious in the cisplatin group and the Feiyanning granule combined with cisplatin group. The expression of MMP-2, MMP-9 and NF-κBp65 in the lung cancer Ning Fang group, the Feiyanning granule group, the Feiyanning granulation group and the cisplatin group was significantly lower than that in the cisplatin group (P <0.05). Conclusion: Feiyanning Granule can obviously improve the quality of life and inhibit tumor metastasis in mice. The mechanism may be to interfere with NF-κB signaling pathway and further regulate tumor-associated macrophages.