慢性阻塞性肺疾病急性加重期患者外周血CD4^＋CD25^＋Foxp3^＋调节性T细胞的变化及其与胰岛素抵抗的关系

目的观察慢性阻塞性肺疾病急性加重期（AECOPD）患者外周血单个核细胞CD4^＋CD25^＋Foxp3^＋调节性T细胞（Treg）的变化，及其与胰岛素抵抗的关系。方法选择79例AECOPD患者，根据肺功能进行疾病严重程度分级（Ⅰ级11例，Ⅱ级31例，Ⅲ级28例，V级9例）。42例健康体检者作为正常对照。检测空腹胰岛素（FINS）及空腹血糖（FBG），计算胰岛素抵抗指数（HOMA-IR）；采用流式细胞术检测患者外周血单个核细胞CD4^＋CD25^＋Foxp3^＋Treg数量，并计算CD4^＋CD25^＋Foxp3^＋Treg占CD4^＋T淋巴细胞的百分比（CD4^＋CD25^＋Foxp3^＋Treg／CD4^＋T）；分析CD4^＋CD25^＋Foxp3^＋Treg与胰岛素抵抗的关系。结果与正常对照组比较，各级AECOPD患者FBG、FINS及HOMA—IR均明显升高（P〈0．01，P〈0．05），外周血单个核细胞CD4^＋CD25^＋Foxp3^＋Treg／CD4^＋T及CD4^＋CD25^＋Foxp3^＋Treg绝对值均明显下降（P〈0．01，P〈0．05）。Ⅲ级和Ⅴ级AECOPD患者较Ⅰ级和Ⅱ级HOMA-IR升高更为明显（P〈0．01，P〈0．05）；而外周血单个核细胞CD4^＋CD25^＋Foxp3^＋Treg／CD4^＋T及CD4^＋CD25^＋Foxp3^＋Treg绝对值逐渐减少，其中Ⅲ级和V级较Ⅰ级和Ⅱ级明显减少（P〈0．01，P〈0．05）。相关分析表明CD4^＋CD25^＋Foxp3^＋Treg／CD4^＋T及CD4^＋CD25^＋Foxp3^＋Treg绝对数均与HOMA-IR呈明显负相关（r值分别为-0．633和-0．871，P〈0．01）。结论AECOPD患者外周血CD4^＋CD25^＋Foxp3^＋Treg数目和比例降低，存在胰岛素抵抗，并与疾病的严重程度相关。CD4^＋CD25^＋Foxp3^＋Treg可能通过调节胰岛素抵抗参与COPD的形成和发展。

The Changes of CD4 + CD25 + Foxp3 + Regulatory T cells in Peripheral Blood of Patients with Acute Exacerbations of COPD and Its Relationship with Insulin Resistance

Objective To investigate the changes of CD4^ ＋ CD25^ ＋ Foxp3 ^＋ regulatory T cells（Treg） in peripheral blood of patients with acute exacerbation of COPD （AECOPD）, and analyze the relationship of CD^＋ CD25^ ＋ Foxp3^＋ Treg with insulin resistance. Methods A total of 79 patients with AECOPD were divided into four groups according to disease severity（ 11 cases in stage Ⅰ ,31 cases in stage Ⅱ,28 cases in stage Ⅲ,an 9 cases in stage Ⅳ ）. 42 healthy volunteers were recruited as control. Fast blood glucose（FBG） and fast insulin（FINS） were measured for calculating the insulin resistance index. The CD4^＋ CD25^＋ Foxp3^＋ Treg were detected by flow cytometry. The relationship between the proportion and number of CD4^＋ CD25^ ＋ Foxp3^ ＋ Treg with insulin resistance was statistically analyzed. Results Compared with the healthy control group, the levels of FBG, FINS, and insulin resistance index in the AECOPD patients were significantly higher （P 〈 0. 01, P 〈 0. 05 ）. The proportion and number of CD4 ~ CD25^ ＋ Foxp3^ ＋ Treg in peripheral blood decreased significantly（ P 〈 0. 01, P 〈 0.05 ）. The insulin resistance index increased with the severity of AECOPD while the proportion and number of CD4^＋ CD25 ＋ Foxp3^ ＋ Treg in peripheral blood decreased. The insulin resistance index in the AECOPD patients of stage III and IV were higher than those of stage I and II. The proportion and number of CD^＋ CD25^＋ Foxp3^＋ Treg in the AECOPD patients of stage Ⅲ and Ⅳ were significantly lower than those of stage Ⅰ and Ⅱ. Both the proportion and number of CD4 ^＋ CD25^＋ Foxp3^＋ Treg were negatively correlated with insulin resistance （ r = - 0. 633, - 0. 871, P 〈 0. 01 ）. Conclusions CD^＋ CD25^＋ Foxp3^＋ Treg cells might may play important role in modulating insulin resistance in AECOPD. The more serious the disease, the lower the CD4^＋ CD25^＋ Foxp3^＋ Treg and the worse insulin resistance.