荷瘤小鼠外周血髓系抑制性细胞的比例与血清转化生长因子-β_1水平的关系

Correlation between percentage count of peripheral myeloid -derived suppressor cells and serum level of TGF-β_1 in tumor bearing mice

目的通过建立小鼠原位肝癌模型,检测荷瘤小鼠外周血髓系抑制性细胞(MDSC)的比例和血清转化生长因子(TGF)-β1水平,探讨其在肝癌发病中的作用机制。方法建立小鼠原位肝癌模型,分离荷瘤小鼠外周血的单个核细胞,流式细胞仪检测荷瘤小鼠不同时间外周血MDSC的比例;酶联免疫吸附试验(ELISA)检测荷瘤小鼠血清TGF-β1水平。以同期正常小鼠作对照。结果荷瘤小鼠外周血MDSC比例明显升高:对照组、模型组7、14、21d外周血MDSC的比例分别为(3.5±2.2)%、(9.4±2.6)%、(16.4±5.6)%、(25.3±11.3)%,除模型组7d与对照组比较差异无统计学意义(P>0.05)外,其余各组与对照组比较均有统计学意义(P<0.05);荷瘤小鼠血清TGF-β1水平明显升高:对照组、模型组7、14、21d血清TGF-β1水平分别为(4.9±1.4)、(14.1±6.0)、(24.0±3.3)、(9.2±1.2)ng/ml。除模型组21d与对照组比较差异无统计学意义(P>0.05)外,其余各组与对照组比较差异均有统计学意义(P<0.05)。外周血MDSC的比例与血清TGF-β1水平呈明显正相关(r=0.564,P<0.05)。结论随着肿瘤的进展,外周血MDSC的比例明显升高,且与血清TGF-β1水平呈明显正相关,提示荷瘤小鼠外周血MDSC的比例与肿瘤的生长进展密切相关,MDSC通过分泌TGF-β1发挥免疫抑制作用,可促进肿瘤的生长与转移。

Objective To investigate the correlation between percentage count of peripheral myeloid-derived suppressor ceils （MDSC） and serum level of transforming growth factor beta 1 （TGF-β1） in entopic hepatocarcinoma mouse model, and to explore the role of MDSC in pathogenesis of liver cancer. Methods Mouse model of entopic liver cancer was established. Peripheral mononuclear cells （PMNCs） were separated from the tumor-bearing mice. At various time points, the percentage of MDSC in PMNCs was analyzed by flow cytometry, the level of serum TGF-β1 were tested by enzyme-linked immunosorbent assay, and these were compared with healthy mice as controls. Results The percentage of MDSC in peripheral blood and the level of serum TGF-β1 were significantly higher than those in control group. On days 7, 14 and 21, the percentages of MDSCs in PMNCs were （3.5±2.2）%, （9.4±2.6）%, （16.4±5.6）% and （25.3±11.3）%. These figures were statistically significant as compared with the controls （P〈0.05） except for on day 7 （P〉0.05）. On days 7, 14 and 21, the serum level of TGF-β1 were （14.1±6.0）, （24.0±3.3） and （9.2±1.2）ng/ml. These figures were statistically significant as compared with the controls [（4.9±1.4）ng/ml, （P〈0.05）] except for on day 21 （P〉 0.05）. There was a significantly positive correlation between MDSC in peripheral blood and serum level of TGF-β1 （r= 0.564, P〈0.05）. Conclusion Along with tumor progression, the percentage of MDSC in PMNCs increased and was positively correlated with serum level of TGF-β1, suggesting a close relationship between percentage count of MDSC and tumor growth, MDSC may promote tumor growth and metastasis through secretion of immunosuppressing TGF-β1.