阻塞性睡眠呼吸暂停低通气综合征患者巨噬细胞移动抑制因子的表达及其与血管内皮细胞损伤的关系研究

The expression of macrophage migration inhibitory factor in obstructive sleep apnea hypopnea syndrome and its injury to endothelial cells

目的 探讨OSAHS患者巨噬细胞移动抑制因子（MIF）的表达及其与血管内皮细胞损伤的关系.方法 选择2014年2月至2015年2月在广东省人民医院门诊或住院首次行多导睡眠监测（PSG）的患者共71例,其中男62例,女9例,根据PSG检查结果分为对照组（20例）、轻度OSAHS组（19例）、中度OSAHS组（15例）及重度OSAHS组（17例）.所有研究对象采取空腹外周静脉血,分离血浆,ELISA法检测血浆中MIF表达水平;再分离重度OSAHS组及对照组患者外周血单个核细胞（PBMC）,并将PBMC与人脐静脉内皮细胞（HUVEC）共培养72 h后,流式细胞仪检测内皮细胞的凋亡,ELISA等法检测培养上清液中内皮素-1（ET-1）、细胞间黏附因子-1（sICAM-1）、一氧化氮（NO）及白细胞介素-6（IL-6）表达水平.结果 血浆中MIF表达水平在对照组及轻、中、重度OSAHS患者分别为（26±8）、（28±9）、（31±14）和（39±15） ng/ml,重度OSAHS组明显高于对照组（P＜0.01）,多组间比较差异有统计学意义（F=15.65,P＜0.001）.MIF与OSAHS严重程度的相关分析结果表明,MIF与呼吸暂停低通气指数（AHI）和氧减指数呈正相关（r=0.365,0.308,均P＜0.05）,而MIF与最低血氧饱和度呈负相关（r=-0.323,P=0.019）.在两组细胞共培养中,对照组和重度OSAHS组内皮细胞凋亡率分别为（2.9±1.0）％和（8.23±3.0）％,差异有统计学意义（=5.97,P＜0.001）.ET-1在对照组和重度OSAHS组表达分别为（7±6）和（10±5）pg/ml,差异无统计学意义（t=3.018,P＞0.05）.sICAM-1在对照组和重度OSAHS组分别为（11±8）和（20±7）ng/ml,差异有统计学意义（t=7.58,P=0.014）.NO在对照组和重度OSAHS组分别为（35±16）和（25±5）μmol/L,差异无统计学意义（t =2.01,P＞0.05）.IL-6在对照组和重度OSAHS组分别为（220±42）和（436±178）μmol/L,差异有统计学意义（t=2.77,P＜0.05）.结论 MIF可能参与OSAHS疾病的炎症过程,并且与其疾病严重程度有关,在血管内皮细胞的损伤中可能起作用.

Objective To study the expression of macrophage migration inhibitory factor （MIF） in obstructive sleep apnea hypopnea syndrome （OSAHS） and its injury to endothelial cells.Methods According to the PSG test results,subjects who were the first time to take PSG examination without treatment （n =71） were divided into a control group （n =20）,a mild OSAHS group （n =19）,a moderate OSAHS group （n =15） and severe OSAHS group （n =17）.For each patients,4 ml fasting peripheral blood was obtained when PSG was finished around 6：30 in the next morning,and the MIF level in plasma was detected with the ELISA method.Peripheral blood mononuclear cells （PBMC） from the control group and the severe OSAHS patients were cocultured with umbilical vein endothelial cells （HUVEC） for 72 hours.The apoptosis of HUVEC was detected by flow cytometry,while ET-1,NO,sICAM-1 and IL-6 in the supernatants were measured with the ELISA method.Results The plasma level of MIF in the control group and the mild,the moderate,and the severe OSAHS patients was （26 ± 8）,（28 ± 9）,（31 ± 14）,（39 ± 15） ng/ml,respectively （F=15.65,P 〈0.001）,and it was higher in the severe OSAHS group as compared to the control group（P 〈0.01）.The level of MIF was associated positively with the apnea hypoventilation index （AHI,r =0.365,P=0.008） and the oxygen index reduction （ODI,r =0.308,P =0.308） n but negatively with the lowest blood oxygen （r =0.323,P =0.323）.Endothelial cell apoptosis rate in the control group and the severe OSAHS group was （2.94 ± 1.02） %,（8.23 ± 3.01） %,respectively,t =5.97,P 〈0.001.ET-1 in the control group and the severe OSAHS group was （6.71 ± 5.52）,（9.88 ± 4.79） pg/ml,respectively,t =3.018,P =0.141.sICAM-1 in the control group and the severe OSAHS group was （11±8）,（20 ±7） ng/ml,respectively,t =7.58,P =0.014.NO in the control group and the severe OSAHS group was （35 ± 16）,（25 ± 5） mol/L,respectively,t =2.01,P =0.067.IL-6 in the control group and the severe OSAHS group was （220 ± 42）,（436 ± 178） mol/L,respectively,t =2.77,P 〈 0.05.Conclusion MIF is closely related to the degree of OSAHS severity,and it may be involved in the development and endothelial injury in OSAHS.