阻塞性睡眠呼吸暂停低通气综合征患者外周单个核细胞肿瘤坏死因子α及NF-κB的表达及关系

The Expression and Relationship of TNF-α and NF-κB in PMBCs of OSAHS Patients

【目的】研究阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者外周血单个核细胞(PBMC)中核因子-κB(NF-κB)以及肿瘤坏死因子α(TNF-α)的表达及其之间的关系。【方法】依据睡眠监测的结果,将实验对象分为正常对照组与OSAHS组,进一步将OSAHS组分为轻、中、重组。采用免疫印迹法(Western blot)测定其PBMC的NF-κB蛋白水平,以逆转录-聚合酶链反应(RT-PCR)对PBMC的TNF-αmRNA半定量,并采用ELISA法检测TNF-α血清水平,而且其中18名进行持续正压气道通气(CPAP)治疗患者测定治疗一月后血清中TNF-α水平。【结果】OSAHS组较对照组PBMC的NF-κB蛋白水平及其TNF-αmRNA水平、TNF-α血清水平的表达有显著性差异,且轻度及中度与重度OSAHS组间PBMC的NF-κB蛋白水平及TNF-αmR-NA水平、TNF-α血清水平的表达均有显著性差异。OSAHS患者PBMC的NF-κB蛋白表达与血清TNF-α水平、PMBC的TNF-αmRNA水平两两间均为正相关,而且OSAHS患者呼吸暂停低通气指数(AHI)与PB-MC的NF-κB蛋白表达、血清TNF-α水平、PBMC的TNF-αmRNA水平均呈显著正相关,最低血氧饱和度(LSaO2)与PBMC的NF-κB蛋白表达亦呈显著正相关。【结论】说明在OSAHS患者中转录因子NF-κB是TNF-α的重要上游调节因子,并促进了TNF-α的表达,从而参与了OSAHS的发病机制。NF-κB蛋白水平在一定程度上预示了疾病的严重程度。

[Objective]To study the TNF-α and NF-κB production of peripheral blood mononuclear cells （PBMCs） in patients with OSAHS and to explore their relationship. [Methods]Based on the results of sleep monitoring,the subjects were divided into two groups：healthy control group and OSAHS group, and the OSAHS group was divided into the mild group, the moderate group and the severe group. The level of NF-κB in PBMCs was tested by Western blot. The serum levels of TNF-α and TNF-α mRNA of PBMCs were determined by ELISA Kits and reverse transcription-polymerase chain reaction （RT-PCR）, respectively. Eighteen patients with severe OSAHS were treated with CPAP for 1 month, and the serum levels of TNF-α were also measured. [Results]The level of NF-κB in PBMCs ,TNF-α mRNA of PBMCs and the serum levels of TNF-α in OSAHS were significantly higher than in the control group. There were significant differences between the mild ,the moderate and the severe group in the level of NF-κB in PBMCs ,TNF-α mRNA of PBMCs and the serum levels of TNF-α. There were positive correlations between the level of NF-κB in PBMCs and TNF-α mRNA of PBMCs, the serum levels of TNF-α respectively. AHI of the OSAHS patients was positively correlated with the level of NF-κB in PBMCs ,TNF-α mRNA of PBMCs and the serum levels of TNF-α. LSaO2 was positively correlated with the level of NF-κB in PBMCs. [Conclusion]NF-κB may be an important upstream regulatory factor and promote the expression of TNF-κB . Simultaneously the expression of NF-κB indicates the degree of OSAHS in a certain extent.