OSAHS患者巨噬细胞移动抑制因子基因表达与疾病严重程度和血管内皮损伤标志物的相关性分析

The expression of macrophage migration inhibitory factor in obstructive sleep apnea hypopnea syndrome and its relationship with the severity and markers of vascular endothelial injury

目的分析阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者巨噬细胞移动抑制因子(MIF)表达与疾病严重程度和血管内皮损伤标志物的相关性。方法选取2015年7月—2016年12月上海交通大学医学院附属新华医院崇明分院呼吸科首次行多导睡眠图(PSG)检查的OSAHS患者62例作为研究对象,依据PSG检测结果,分为轻度OSAHS组(20例)、中度OSAHS组(21例)和重度OSAHS组(21例),另选取正常志愿者20例作为健康对照组。所有研究对象采取空腹外周静脉血,PCR法检测MIF基因表达情况,ELISA法检测血浆中MIF、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、可溶性血管细胞黏附分子-1(sVCM-1)、血管性血友病因子(vWF)、内皮素(ET)等因子水平;比较分析MIF与IL-6、TNF-α、sVCM-1、vWF、ET等因子的相关性。结果实时荧光定量PCR结果显示:轻、中、重度OSAHS组及健康对照组血浆中MIF基因表达水平分别为(4.55±0.82)、(5.23±0.75)、(8.14±1.21)、(3.78±0.66),组间比较差异有统计学意义(F=20.581,P=0.000),其中重度OSAHS患者血浆中MIF基因表达水平明显高于健康对照组(t=5.31,P<0.05);ELISA法检测结果显示:轻、中、重度OSAHS患者及健康对照组血浆中MIF水平分别为(22.2±3.6)、(25.8±3.2)、(32.5±4.7)、(21.6±3.1)ng/ml,组间比较差异有统计学意义(F=23.226,P=0.000),其中重度OSAHS患者血浆MIF水平明显高于健康对照组(P<0.05),ELISA法与实时荧光定量PCR检测结果趋势一致。AHI、氧减指数在健康对照组及轻度、中度、重度OSAHS组中表达依次升高,组间比较差异均有统计学意义(P<0.01);最低血氧饱和度依次降低,组间比较差异有统计学意义(P<0.05)。IL-6、TNF-α、CRP、sVCM-1、vWF、ET在健康对照组及轻度、中度、重度OSAHS组中表达分别依次升高,组间比较差异有统计学意义(P<0.05)。Pearson相关分析显示,OSAHS患者严重程度与MIF表达呈正相关;MIF表达与AHI、氧减指数、sVCM-1、vWF、ET呈正相关(r=0.612、0.526、0.568、0.711、0.688,P<0.05),与最低血氧饱和度呈负相关(r=-0.663,P<0.05)。结论 MIF在OSAHS患者血浆中高表达,与患者疾病严重程度相关,可能参与了OSAHS疾病的炎性反应过程,在血管内皮细胞的损伤中可能起一定的作用。

Objective To investigate the expression of macrophage migration inhibitory factor （MIF） in obstructive sleep apnea hypopnea syndrome （OSAHS） and its relationship with the severity and markers of vascular endothelial injury. Methods Patients （n = 62 ） who were the first time to take PSG examination without treatment were divided into a mild OS- AHS group （ n = 20）, a moderate OSAHS group （n = 21 ） and a severe OSAHS group （ n = 21 ） according to the PSG test resuits. And we got a volunteer group （ n =20） whose PSG test results were normal as a control group. Peripheral venous plasma of all the patients was collected and separated; The expression levels of MIF, IL-6 ,TNF-c~, CRP, sVCM-1, vWF and endo- thelin were tested by EL1SA or RT PCR; analyze the relationship of MIF and IL-6, TNF-α, CRP, sVCM-1, vWF, endothe- lin. Results Real time FCR showed the levels of MIF in volunteer, mild OSAHS, moderate OSAHS and severe OSAHS group were （4.55 ±0. 82）, （ 5.23± 0.75 ）, （ 8.14 ±1. 21 ）, （ 3.78 ±0.66） respectively, and the differences between groups were statistically significant （ F = 20. 581 ,P = 0. 000 ） ; MIF gene expression （ Real time PCR） level in severe OSAHS group was higher than that of control group （P 〈 0.05 ）, and the ROC curve area was 0. 825 （95% CI 0. 780-0.912） ; the results of ELISA was in line with Real time PCR; Pearson analysis showed the expression of plasma MIF in moderate OSAHS group was only positively correlated with AHI, while it was positively correlated with AHI and oxygen index reduction （ODI）, but nega- tively correlated with lowest blood oxygen according to the Pearson correlation analysis （ all P 〈 0.05 ） ; the expression of plas- ma MIF in moderate OSAHS group was positively correlated with IL-6, vWF and endothelin, while it was positively correlated with IL-6, TNF-o~, CRP, sVCM-1, vWF and endothelin （ r = O. 612,0.526,0.568,0.711,0. 688, all P 〈 0.05）. Conclusion MIF is highly expressed in the plasma of the OSAHS patients and MIF is closely related to the degree of OSAHS severity, and it may be involved in the development and work in endothelial injury in OSAHS.