不同分期前列腺癌患者外周血CD4^+ CD25^+ Foxp3^+调节性T细胞的变化及与胰岛素抵抗的相关性  

Changes of CD4^+ CD25^+ Foxp3^+ regulatory T cells in the peripheral blood and their correlation with insulin resistance in different stages of prostate cancer

作　　者：章步文[1] 黎钢[1] 叶津津[1] 李峥嵘[1] 

机构地区：[1]湖州市中医院肿瘤内科,浙江湖州313000

出　　处：《中华男科学杂志》2015年第5期420-423,共4页National Journal of Andrology

摘　　要：目的 :观察不同分期前列腺癌患者外周血单个核细胞CD4+CD25+Foxp3+调节性T细胞的变化及与胰岛素抵抗的关系。方法:采用流式细胞术检测62例前列腺癌患者(患者组,临床TNM分期Ⅰ期5例、Ⅱ期16例、Ⅲ期21例、Ⅳ期20例)外周血单个核细胞(PBMC)中CD4+CD25+Foxp3+调节性T细胞数目,计算CD4+CD25+Foxp3+调节性T细胞占CD4+T淋巴细胞的百分率;并检测其空腹胰岛素及空腹血糖水平,计算胰岛素抵抗指数(HOMA-IR);采用ELISA法测定外周血胰岛素样生长因子1(IGF-1)水平,分析CD4+CD25+Foxp3+调节性T细胞与胰岛素抵抗的相关性,并与42例健康体检者进行对照。结果:与健康对照组相比,前列腺癌患者HOMAIR明显升高(6.68±1.66 vs 3.68±1.42),IGF-1水平明显下降[(96.39±21.21)ng/ml vs(164.56±30.58)ng/ml],PBMC CD4+CD25+Foxp3+Treg占CD4+T淋巴细胞的百分率[(13.88±0.96)%vs(5.33±0.65)%]及CD4+CD25+Foxp3+Treg绝对值[(3.55±0.29)×107vs(1.99±0.78)×107]明显升高(P<0.05,P<0.01)。患者PBMC CD4+CD25+Foxp3+Treg占CD4+T淋巴细胞的百分率及CD4+CD25+Foxp3+Treg绝对数﹑HOMA-IR均随TNM分期逐渐加重而增加,IGF-1逐渐下降;相关性分析表明:CD4+CD25+Foxp3+Treg/CD4+T及CD4+CD25+Foxp3+Treg绝对数均与HOMA-IR呈明显正相关(r分别为0.689、0.722,P<0.01),与IGF-1呈明显负相关(r分别为-0.896、-0.747,P<0.01)。结论:前列腺癌患者存在不同程度的胰岛素抵抗,且随着疾病程度的加重,外周血CD4+CD25+Foxp3+调节性T细胞数目和比例及胰岛素抵抗逐渐加重;CD4+CD25+Foxp3+调节性T细胞可能通过调节胰岛素抵抗参与其形成和发展。Objective：To investigate the changes of CD4＋CD25＋Foxp3＋regulatory T cells in the peripheral blood mononuclear cells（ PBMC） and their association with insulin resistance in different stages of prostate cancer（ PCa）.Methods：Using flow cytometry,we counted the CD4＋CD25＋Foxp3＋regulatory T cells in the PBMCs of 62 PCa patients（5 cases of TNM stageⅠ,16 cases of stage Ⅱ,21 cases of stage Ⅲ,and 20 cases of stage Ⅳ） and 42 normal healthy controls,and calculated their proportion in the CD4＋T-lymphocytes.We determined the levels of fast blood glucose（FBG） and fast insulin（FINS） for the insulin resistance index（HOMA-IR）,obtained the serum IGF-1 level by ELISA,and analyzed the relationship of the count and proportion of CD4＋CD25＋Foxp3＋regulatory T cells with insulin resistance by comparison between the PCa patients and normal healthy controls.Results：Compared with the control group,the PCa patients showed significantly increased HOMA-IR（3.68 ± 1.42 vs 6.68 ± 1.66）,decreased level of serum IGF-1（[164.56 ± 30.58] vs [96.39 ± 21.21] ng / ml）,and elevated count（[1.99 ± 0.78]× 107 vs [3.55 ± 0.29] × 107） and proportion（[5.33 ± 0.65] vs [13.88 ± 0.96]%） of CD4＋CD25＋Foxp3＋regulatory T cells in the PBMCs.The TNM stage was correlated positively with the count and percentage of CD4＋CD25＋Foxp3＋regulatory T cells and HOMA-IR,but negatively with the level of serum IGF-1.Meanwhile,the count and percentage of CD4＋CD25＋Foxp3＋regulatory T cells were found to have a positive correlation with HOMA-IR（ r = 0.722 and 0.689,P 〈0.01） but a negative correlation with the level of serum IGF-1（ r =- 0.747 and- 0.896,P 〈0.01）.Conclusion：The count and proportion of CD4＋CD25＋Foxp3＋regulatory T cells in the peripheral blood and insulin resistance increase with the elevated stage of PCa.CD4＋CD25＋Foxp3＋regulatory T cells may be involved in the occurrence and progression of PCa by regulating insulin resistance.

关 键 词：前列腺癌 胰岛素抵抗 调节性T细胞 流式细胞术 

分 类 号：R737.25[医药卫生—肿瘤]