十全大补汤抑制Lewis肺癌原发瘤切除后转移瘤的研究

Inhibitory Effect of Shiquan Dabu Tang on Lewis Pulmonary Metastasis after Primary Tumor Excision in Mice

目的:探讨十全大补汤对小鼠Lewis肺癌原发瘤(先前接种肿瘤)切除后转移瘤生长及血管生成的影响,并探讨可能的机制。方法:构建C57/BL6小鼠Lewis肺癌肺转移模型,随机分为原发瘤切除组(TR)、原发瘤未切除组(TP)、十全大补汤组(Shiquan Dabu Tang group,SDT)。采用切除原发瘤及十全大补汤31.2 g·kg-1治疗10 d,摘除眼球取血,剥出肺脏,应用组织切片苏木素-伊红染色法,观察肺部转移瘤情况。链霉菌抗生物素蛋白-过氧化物酶连结(SP)免疫组织化学法检测转移瘤微血管密度(MVD)及细胞增殖。酶联免疫吸附测定法(ELISA)检测治疗后小鼠血清中血管内皮生长因子(VEGF)、血管抑素(AS)和内皮抑素(ES)的表达水平。结果:治疗10 d后,小鼠肺转移灶数与原发瘤切除组(47.30±5.57)个比较,十全大补汤组(8.28±5.28)个及原发瘤未切除组(10.71±3.30)个均明显降低(P<0.01);小鼠肺脏质量与原发瘤切除组(0.57±0.05)g比较,十全大补汤组(0.26±0.05)g及原发瘤未切除组(0.28±0.05)g均明显降低(P<0.01)。原发瘤切除组、原发瘤未切除组和十全大补汤组转移瘤Ki67表达分别为(55.10±6.51)%,(34.60±4.95)%,(27.10±4.56)%,CD34表达分别为(35.40±2.46)%,(30.60±6.54)%,(22.09±5.89)%,十全大补汤组降低明显,差异有统计学意义(P<0.01)。ELISA检测显示,与原发瘤切除组比较,十全大补汤能够降低血清中VEGF及上调ES的表达,差异具有统计学意义(P<0.01)。结论:原发瘤切除可使荷瘤小鼠体内的VEGF和ES比例失衡,有利于肿瘤血管生成及促进转移。十全大补汤明显抑制小鼠原发瘤切除后转移瘤生长,明显抑制转移瘤血管生成以及与之相关的血管生成调节因子的作用。

Objective：To investigate the effects of Shiquan Dabu Tang on Lewis pulmonary metastasis angiogenesis and pulmonary metastasis after primary tumor excision,and explore its possible mechanism and clinical significance.Method： The C57/BL6 mouse Lewis pulmonary metastasis model was established,and mice randomly divided into primary tumor resection group（TR）,primary tumor preserve group（TP） and Shiquan Dabu Tang group（SDT）.Microvessel density（MVD） and cell multiplication of pulmonary metastasis was detected with SP immunohistochemical staining.The level of vascular endothelial growth factor（VEGF）,angiostatin（AS） and endostatin（ES） was examined by ELISA assay.Result： The number of pulmonary metastasis,incidence of metastases and MVD were evidently inhibited by Shiquan Dabu Tang.Ki67 expression was significantly lower than control group.Conclusion： The excision of primary tumor can promote pulmonary metastasis angiogenesis and pulmonary metastasis,and application of Shiquan Dabu Tang after operation has instructive clinical significance in preventing tumor metastasis.