福多司坦对重度阻塞性睡眠呼吸暂停综合征患者Th1、Th2细胞以及血清中IFN-γ和IL-4的影响

Effect of fudosteine on proportions of Th1 and Th2 lymphocytes and serum levels of IFN-γ and IL-4 in patients with severe obstructive sleep apnea syndrome

摘要:

目的 探讨福多司坦对阻塞性睡眠呼吸暂停综合征（OSAS）患者Th1、Th2细胞的比例以及血清中γ干扰素（IFN-γ）和白细胞介素?4（IL-4）浓度的影响。方法 选择2013年4月至2014年12月在南京医科大学附属无锡市人民医院呼吸科就诊的门诊以及住院的重度OSAS患者57例和单纯打鼾患者20例，所有受试者均为男性，年龄55～76（67.0±6.4）岁。按照呼吸暂停低通气指数（AHI，次/h）将患者分为3组，即对照组（AHI≤5，n＝20）、OSAS组（AHI＞40，n＝28）和OSAS＋福多司坦组（AHI＞40，口服福多司坦片2周，n＝29）。采用流式细胞检测法测定Th1和Th2细胞所占的比例；酶联免疫吸附法测定血清中IFN-γ和IL-4的浓度。结果 研究结果表明，3组患者的年龄和体质量指数（BMI）差异无统计学意义（P＞0.05）。与对照组相比，OSAS组患者Th1细胞所占比例显著升高[F（2，74）＝85.06，P＜0.01]，同时Th1细胞相关的细胞因子IFN-γ的浓度也明显上升[F（2，74）＝131.4，P＜0.01]；与OSAS组相比，OSAS＋福多司坦组患者Th1细胞所占比例显著下降[F（2，74）＝85.06，P＜0.01]，血清中IFN-γ的浓度也明显下调[F（2，74）＝131.4，P＜0.01]；而3组患者Th2细胞的比例[F（2，74）＝2.66，P＝0.08]和血清中IL-4的水平[F（2，74）＝2.29，P＝0.11]的差异无统计学意义。结论 重度OSAS患者体内Th1细胞的激活程度显著升高，表现为相关细胞因子分泌的增多，而Th2细胞及相关细胞因子的变化不明显。福多司坦可以抑制Th1的过度激活，并降低Th1相关细胞因子的分泌。

Abstract:

Objective To determine the effect of fudosteine on the percentages of Th1 and Th2 cells and the serum levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in severe obstructive sleep apnea syndrome (OSAS) patients. Methods Fifty-seven severe OSAS in- and out-patients and 20 simple snorers who were treated in the Wuxi People’s Hospital from April 2013 to December 2014 were recruited in this study. All the participants were male, and aged from 55 to 76 (67.0±6.4) years. According to apnea hypopnea index (AHI), the cohort was divided into 3 groups, that is, control group (simple snorers, AHI≤5, n＝20), OSAS group (AHI＞40, n＝28) and OSAS＋fudosteine group (AHI＞40, taking fudosteine for 2 weeks, n＝29). The proportions of Th1 and Th2 cells were detected by flow cytometry, while the serum contents of IFN-γ and IL-4 were evaluated by ELISA. Results There was no significant difference in the age and body mass index (BMI) among the 3 groups (P＞0.05). Compared with the control group, the proportion of Th1 was increased obviously in OSAS group [F(2,74)＝85.06, P＜0.01], meanwhile, the level of IFN-γ (Th1 related cytokine) was also significantly elevated [F(2,74)＝131.4, P＜0.01]. Compared with OSAS group, both the proportion of Th1 [F(2,74)＝85.06, P＜0.01] and level of IFN-γ [F(2,74)＝131.4, P＜0.01] were decreased markedly in OSAS＋fudosteine group. However, there was no statistical difference in the proportion of Th2 cells [F(2,74)＝2.66, P＝0.08] and serum level of IL-4 [F(2,74)＝2.29, P＝0.11] among the 3 groups. Conclusion Th1 cells are activated obviously in the patients with severe OSAS, and more Th1 related cytokines are secreted, while, no obvious alternations of Th2 cells and related cytokine are found. Fudosteine inhibits the excessive activation of Th1 cells and excessive secretion of Th1 related cytokine.