阻塞性睡眠呼吸暂停低通气综合征患者单个核细胞对血管内皮细胞凋亡的影响  

Effect of peripheral blood mononuclear cells from patients with obstructive sleep apnea-hypopnea syndrome on apoptosis of vascular endothelial cells

作　　者：叶春幸[1] 高兴林[1] 欧琼[2] 李东风[3] 岑瑞金[2] 周茂华[4] 

机构地区：[1]广东省人民医院东病区呼吸科,广州广东省老年医学研究所510080 [2]广东省人民医院睡眠实验室,广州510080 [3]广东省人民医院医学研究中心,广州510080 [4]广东省人民医院流式细胞仪室,广州510080

出　　处：《中华医学杂志》2007年第31期2181-2184,共4页National Medical Journal of China

基　　金：广东省科技公关资助项目(2005B30601009)

摘　　要：目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血管内皮细胞的损伤机制。方法按多导睡眠监测仪检查结果将研究对象分为正常对照组(n=20)、轻度 OSAHS 组(n=21)、中度 OSAHS 组(n=24)和重度 OSAHS 组(n=20)。所有研究对象睡醒后(约6点30分左右)采外周静脉血,分离单个核细胞(MNC)。分离的 MNC 与人脐静脉内皮细胞 ECV304共同培养48 h,培养后收集上清液及内皮细胞,ELISA 检测上清液中的 TNF-α、IL-6,流式细胞仪检测内皮细胞的凋亡率、Fas 蛋白表达。结果正常对照组、轻、中及重度 OSAHS 患者 MNC 细胞产生肿瘤坏死因子α(TNF-α)分别为(0.80±0.10)μg/L、(1.20±0.30)μg/L、(1.40±0.50)μg/L 及(2.10±0.60)μg/L,多组比较(F=69.65,P<0.01);产生白细胞介素6(IL-6)分别为(23.50±6.50)μg/L、(49.60±2.80)μg/L、(46.90±10.80)μg/L 及(64.80±9.90)μg/L,多组比较(F=182.83,P<0.01)。MNC 细胞产生 TNF-α及 IL-6均高于正常对照组(均 P<0.01);而重度 OSAHS 患者 MNC 产生 TNF-α及 IL-6均高于轻度及中度(均 P<0.01),轻度与中度 OSAHS 患者之间差异无统计学意义。内皮细胞的凋亡率:正常对照组、轻、中及重度 OSAHS 患者分别为8.3%±3.2%、9.2%±3.0%、19.3%±6.3%及19.6%±3.8%,多组比较(F=39.36,P<0.01);中、重度 OSAHS 患者较正常对照组升高(P<0.01);而轻度 OSAHS 患者与正常对照组比较,中度与重度 OSAHS 患者组比较,差异均无统计学意义。内皮细胞表达 Fas 蛋白各组间差异无统计学意义。内皮细胞凋亡率与 OSAHS 患者 AHI 呈正相关(r=0.589 13,P=0.0106)、与夜间最低血氧饱和度呈负相关(r=-0.507 37,P<0.01)。结论 OSAHS患者血管内皮细胞损伤过程中,单个核细胞可能起重要作用,且这种作用同病情严重程度、夜间缺氧密切相关。Objective To investigate the mechanism of vascular endothelial cell injury in patients with obstructive sleep apnea-hypopnea syndrome （OSAHS）. Methods Peripheral blood samples were collected early in the morning from 20 normal persons, 21 patients with mild OSAHS, 24 patients with moderate OSAHS, and 20 patients with severe OSAHS according to the results of polysomnography （PSG）. Mononuclear cells （MNCs） were isolated and co-cultured with human umbilical vein endothelial cells of the strain ECV304 for 48 h. The levels of tumor necrosis factor （ TNF）-α and interleukin （IL） -6 in the supematant were measured by ELISA, and the apoptosis rate and the protein expression level of Fas of the endothelial cells were detected by flow cytometry. Results The TNF-α level of the severe OSAHS group was （2. 10 ±0. 60） μg/L, significantly higher than those of the moderate OSAHS, mild OSAHS, and normal control groups [ （1.40 ±0.50）μg/L, （1.20±0. 30）μg/L , and （0.80±0. 10 ） μg/L ,F=69.65,P〈 0. 01]. The IL-6 level of the severe OSAHS group was（64. 80±9.90） μg/L, significantly higher than those of the moderate OSAHS, mild OSAHS, and normal control groups [ （46. 90 ± 10. 80）μg/L, （49. 60 ±2. 80） μg/L , and （23.50±6.50） μg,/L ,F = 182. 83 ,P 〈0. 01 ]. The TNF-α and IL-6 levels of the severe OSAHS group were both significandy higher than those of the moderate and mild OSAHS groups （ both P 〈 0. 01 ）. However, there was no significant differences in the TNF-α and IL-6 levels between the mild and moderate OSAHS groups （ both P 〉 0. 05 ） . The apoptosis rates of endothelial cells in the severe and moderate OSAHS groups werel9. 6%± 3.8% and 19. 3% ± 6. 3% respectively, both significandy higher than those of the mild OSAHS and control groups （9.2% ±3. 0% and 8. 3% ± 3. 2% （ both P 〈 0. 01 ） whereas there were no significant differences between the mild OSAHS group and control group and between the moderate OSAHS group and severe group （ both

关 键 词：睡眠呼吸暂停 阻塞性 内皮 血管 单个核细胞 肿瘤坏死因子 白细胞介素6 

分 类 号：R766[医药卫生—耳鼻咽喉科]