低剂量环磷酰胺对黑素瘤荷瘤小鼠体内免疫抑制微环境的干预作用

发布时间：2019-07-23 11:37

【摘要】：目的:检测低剂量环磷酰胺(cyclophosphamide,CYC)腹腔注射对黑素瘤荷瘤小鼠体内微环境中调节性T细胞(regulatory T cells,Treg)、免疫抑制因子白细胞介素-10(interleukin-10,IL-10)及转化生长因子-β(transforming growth factor beta,TGF-β)水平的影响,探讨CYC介导抑制肿瘤微环境的分子机制。方法:建立小鼠荷黑素瘤B16细胞模型,模型鼠随机分为实验组(CYC腹腔注射,每只20 mg/kg)和对照组(同体积0.9%NaCl溶液腹腔注射)。注射前和注射后1、4、7、11和15 d,用流式细胞仪检测小鼠外周血和瘤组织内CD4+CD25+Foxp3+Treg百分率;ELISA法检测血清和肿瘤组织中IL-10和TGF-β水平;观察比较各组荷瘤小鼠的肿瘤生长情况。结果:与对照组相比,实验组小鼠外周血和肿瘤组织中Treg百分率以及IL-10和TGF-β表达水平均明显降低(P0.05);实验组小鼠外周血及肿瘤组织中Treg百分率和IL-10水平变化均正相关(外周血:rs=0.943,P=0.005;肿瘤组织:rs=0.812,P=0.050)。2组小鼠肿瘤生长差异无统计学意义(P0.05)。结论:腹腔注射低剂量CYC可降低荷瘤小鼠外周血和肿瘤组织中Treg百分率和免疫抑制因子IL-10、TGF-β水平,从而有效干预荷瘤小鼠体内免疫抑制微环境,但对肿瘤生长无明显抑制作用。
[Abstract]:Aim: to investigate the effects of low dose cyclophosphamide (cyclophosphamide,CYC) intraabdominal injection on the levels of regulatory T cell (regulatory T cells,Treg, immunosuppressive factor IL-10 (interleukin-10,IL-10) and transforming growth factor-尾 (transforming growth factor beta,TGF- 尾) in melanoma tumor-bearing mice, and to explore the molecular mechanism of CYC-mediated inhibition of tumor microenvironment. Methods: the mouse model of bearing melanoma B16 cells was established. The model mice were randomly divided into experimental group (CYC intraabdominal injection, 20 mg/kg each) and control group (intraabdominal injection of 0.9%NaCl solution of the same volume). Before and 1, 4, 7, 11 and 15 days after injection, the percentage of CD4 CD25 Foxp3 Treg in peripheral blood and tumor tissue of mice was detected by flow cytometry, the levels of IL-10 and TGF- 尾 in serum and tumor tissue were detected by ELISA, and the tumor growth of tumor-bearing mice in each group was observed and compared. Results: compared with the control group, the percentage of Treg and the expression of IL-10 and TGF- 尾 in peripheral blood and tumor tissue of the experimental group were significantly lower than those of the control group (P 0.05), while the percentage of Treg and the level of IL-10 in the peripheral blood and tumor tissue of the experimental group were positively correlated (peripheral blood: rs=0.943,P=0.005; tumor tissue: rs=0.812,P=0.050). There was no significant difference in tumor growth between the two groups (P 0.05). Conclusion: intraabdominal injection of low dose CYC can decrease the percentage of Treg and the level of immunosuppressive factor IL-10,TGF- 尾 in peripheral blood and tumor tissue of tumor-bearing mice, thus effectively interfering with the immunosuppressive microenvironment of tumor-bearing mice, but has no obvious inhibitory effect on tumor growth.
【作者单位】：河北医科大学第二医院小儿外科;
【基金】：河北省科技支撑计划项目(编号:10246139D)
【分类号】：R739.5

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