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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 effect of Shiquandabu Decoction on the growth and angiogenesis of the metastatic tumor after the resection of Lewis lung carcinoma (previously inoculated tumor) in mice and to explore the possible mechanism. Methods: The lung metastasis model of Lewis lung carcinoma in C57 / BL6 mice was established and randomly divided into primary tumor excision group (TR), primary tumor excision group (TP), Shiquan Dabu Tang group (SDT) . The patients were treated with 31.2 g · kg-1 of primary tumor and Shiquanbutu Decoction for 10 days. Blood was removed from the eye and the lungs were stripped. Tissue sectioned hematoxylin-eosin staining was used to observe the metastases of the lungs. Streptomycin avidin - peroxidase linked (SP) immunohistochemistry was used to detect MVD and cell proliferation. The serum levels of vascular endothelial growth factor (VEGF), angiostatin (AS) and endostatin (ES) were detected by enzyme linked immunosorbent assay (ELISA). Results: After 10 days of treatment, the number of lung metastases in mice was significantly lower than that in the primary tumor resection group (47.30 ± 5.57), that in the Shiquan Dabu Tang group (8.28 ± 5.28) and the primary tumor unresectable group (10.71 ± 3.30 ) Were significantly decreased (P <0.01). Compared with the primary tumor resection group (0.57 ± 0.05) g, the shuntu group (0.26 ± 0.05) g and the primary tumor group without resection ± 0.05) g were significantly lower (P <0.01). The expression of Ki67 in primary tumor resection group, primary tumor excision group and Shiquan Dabu Tang group were (55.10 ± 6.51)%, (34.60 ± 4.95)%, (27.10 ± 4.56)%, respectively (35.40 ± 2.46)%, (30.60 ± 6.54)% and (22.09 ± 5.89)%, respectively, and decreased significantly in Shiquan Dabu Tang group. The difference was statistically significant (P <0.01). Compared with the primary tumor resection group, Shiquan Dabu Tang decoction could reduce the serum VEGF and up-regulate the expression of ES, the difference was statistically significant (P <0.01). Conclusion: Primary tumor resection can make the imbalance of VEGF and ES in tumor-bearing mice, which is good for tumor angiogenesis and metastasis. Shiquandabu Decoction significantly inhibited the growth of metastatic tumor after primary tumor resection in mice and significantly inhibited the angiogenesis of metastatic tumor and the related angiogenesis regulators.