天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (1): 19-22.doi: 10.11958/20150161

• 专题研究呼吸系统疾病 • 上一篇    下一篇

阻塞性睡眠呼吸暂停患者外周血内皮祖细胞及 促血管生成因子水平研究

薛艳超1 ， 孙蓓2 ， 王新1 ， 冯靖1△， 曹洁1△   

  1.  目的 观察阻塞性睡眠呼吸暂停 （OSA） 患者外周血内皮祖细胞 （EPC） 不同亚族和促血管生成因子水平的变化， 探讨不同程度 OSA 患者外周血 EPC 对血管修复的可能性。方法 选取 90 例 OSA 患者和 30 例健康志愿者 (对照组)， 根据睡眠呼吸暂停低通气指数(AHI)将 90 例 OSA 患者均分为轻、 中、 重度 OSA 组。密度梯度离心法提取单个核细胞， 依据乙醛脱氢酶(ALDH)活性对 EPC 进行分选， 流式细胞仪联合 CD133、 CD34、 含激酶域插入片段受体 (PE-KDR)相应细胞表面标志物测定 CD133+ KDR+ EPC 及 CD133+ CD34+ EPC、 CD34+ KDR+ EPC、 ALDHlo CD34+ KDR+ EPC 的水平。酶联免疫吸附试验(ELISA)测定患者外周血低氧诱导因子-1α(HIF-1α)， 血管内皮生长因子(VEGF)及基质细胞衍生因子-1α(SDF-1α)的水平。结果 对于外周血 CD133+ KDR+ EPC、 CD133+ CD34+ EPC、 CD34+ KDR+ EPC 水平， 重度 OSA 组>中度 OSA 组>轻度 OSA 组>对照组 （均 P < 0.05）； 轻、 中度 OSA 组的外周血 ALDHlo CD34+ KDR+ EPC 水平高于对照组， 重度 OSA 组低于其他 3 组 （均 P < 0.05）； 血清 HIF-1α、 VEGF 均是重度 OSA 组>中度 OSA 组>轻度 OSA 组>对照组， SDF-1α水平为重度 OSA 组<中度 OSA 组<轻度 OSA 组<对照组 （均 P < 0.05）。结论 OSA 患者可能都会诱导动员并招募大量无效 EPC， 其数量庞大， 但直接参与修复内皮的 ALDHlo CD34+ KDR+ EPC 并未增加， 尤其对于重度 OSA 患者甚至有可能减少， OSA 减弱了修复内皮的可能性， 加重了内皮损伤， 从而增加心血管事件的发生风险。
  • 收稿日期:2015-09-15 修回日期:2015-10-15 出版日期:2016-01-15 发布日期:2016-01-15
  • 通讯作者: △通讯作者 E-mail:zyyhxkfj@126.com; tjcaojie@sina.com E-mail:xych1213@126.com
  • 作者简介:薛艳超(1988)， 女， 硕士在读， 主要从事睡眠低氧性疾病研究
  • 基金资助:
    国家自然科学基金资助项目 （81270144， 30800507， 81570084,2015BAI12B00， 2012BAI05B02）

T Endothelial progenitor cells (EPCs) and promote angiogenesis factor levels in peripheral blood in patients with obstructive sleep apnea

XUE Yanchao1 , SUN Bei 2 , WANG Xin1 , FENG Jing1△, CAO Jie1△   

  1. Abstract： Objective To explore the repair possibilities of endothelial progenitor cells (EPCs）in peripheral blood in patients with different extents of obstructive sleep apnea (OSA) through measuring the levels of pro-angiogenic factors and different subgroups EPCs in peripheral blood in patients with OSA. Methods Ninety adult patients with OSA, 30 healthy controls with matched age and gender were enrolled for this study. The subjects performed Polysomnography, were divided in? to four group based on Apnea Hypopnea Index (AHI). The serum levels of HIF-1α, SDF-1α and VEGF were assessed by ELISA. Mononuclear cells were isolated from peripheral blood with density gradient centrifugation, and flow cytometry was used to detect levels of CD133+ KDR+ EPC, CD133+ CD34+ EPC, CD34+ KDR+ EPC and ALDHlo CD34+ KDR+ EPC based on AL? DH activity, and CD133, CD34, PE-KDR related cell surface markers. Results The levels of CD133+ KDR+ EPC, CD133+ CD34+ EPC, CD34+ KDR+ EPC were higher in OSA groups than those of control group, both of which were higher in severe OSA group than those of in mild and moderate OSA groups. The levels of ALDHlo CD34+ KDR+ EPC were higher in mild and moderate OSA groups than that of the control groups, and the levels of ALDHlo CD34+ KDR+ EPC were significantly lower in se? vere OSA group than those of control, mild and moderate OSA groups. Serum levels of HIF-1α. VEGF were significantly high? er in OSA groups compared to those in control groups, both of which were higher in severe OSA group than those of mild and moderate OSA groups. Serum levels of SDF-1α were significantly lower in severe OSA groups than those of mild, moderate OSA and control groups (P < 0.05). Conclusion The mobilization and recruitment of different subtypes of EPCs are obvious? ly increased in patients with OSA, but ALDHlo CD34+ KDR+ EPC with vascular repair capacity keeps to invariability, even de?creases in patients with severe OSA, which results in endothelial damage, and increases the risk of cardiovascular disease.
  • Received:2015-09-15 Revised:2015-10-15 Published:2016-01-15 Online:2016-01-15
  • Contact: △Corresponding Author E-mail: zyyhxkfj@126.com; tjcaojie@sina.com E-mail:xych1213@126.com

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摘要： 摘要： 目的 观察阻塞性睡眠呼吸暂停 （OSA） 患者外周血内皮祖细胞 （EPC） 不同亚族和促血管生成因子水平的变化， 探讨不同程度 OSA 患者外周血 EPC 对血管修复的可能性。方法 选取 90 例 OSA 患者和 30 例健康志愿者 (对照组)， 根据睡眠呼吸暂停低通气指数(AHI)将 90 例 OSA 患者均分为轻、 中、 重度 OSA 组。密度梯度离心法提取单个核细胞， 依据乙醛脱氢酶(ALDH)活性对 EPC 进行分选， 流式细胞仪联合 CD133、 CD34、 含激酶域插入片段受体 (PE-KDR)相应细胞表面标志物测定 CD133+ KDR+ EPC 及 CD133+ CD34+ EPC、 CD34+ KDR+ EPC、 ALDHlo CD34+ KDR+ EPC 的水平。酶联免疫吸附试验(ELISA)测定患者外周血低氧诱导因子-1α(HIF-1α)， 血管内皮生长因子(VEGF)及基质细胞衍生因子-1α(SDF-1α)的水平。结果 对于外周血 CD133+ KDR+ EPC、 CD133+ CD34+ EPC、 CD34+ KDR+ EPC 水平， 重度 OSA 组>中度 OSA 组>轻度 OSA 组>对照组 （均 P < 0.05）； 轻、 中度 OSA 组的外周血 ALDHlo CD34+ KDR+ EPC 水平高于对照组， 重度 OSA 组低于其他 3 组 （均 P < 0.05）； 血清 HIF-1α、 VEGF 均是重度 OSA 组>中度 OSA 组>轻度 OSA 组>对照组， SDF-1α水平为重度 OSA 组<中度 OSA 组<轻度 OSA 组<对照组 （均 P < 0.05）。结论 OSA 患者可能都会诱导动员并招募大量无效 EPC， 其数量庞大， 但直接参与修复内皮的 ALDHlo CD34+ KDR+ EPC 并未增加， 尤其对于重度 OSA 患者甚至有可能减少， OSA 减弱了修复内皮的可能性， 加重了内皮损伤， 从而增加心血管事件的发生风险。

关键词: 阻塞性睡眠呼吸暂停；, 低氧诱导因子-1α；, 基质细胞衍生因子-1α； , 血管内皮细胞生长因子；, 间歇低氧；, 内皮祖细胞； , 乙醛脱氢酶

Abstract: [Abstract] Objective Hypoxia is one of critical pathophysiological element in obstructive sleep apnea (OSA). Intermittent hypoxia (IH) induced endothelial cells, and enhanced the activity of promoting vascular growth factor. Endothelial progenitor cells (EPCs) of mobilization and recruitment repaired damaged vascular. EPC with low acetaldehyde dehydrogenase (ALDH) activity (ALDHlo EPC) showed the reparation ability. In this study, measuring the serum levels of hypoxia-inducible factor-1α (HIF-1?), plasma stromal cell-derived factor-1α (SDF-1?), vascular endothelial growth factor (VEGF) and levels of different subgroups EPC in peripheral blood in patients with OSA. To explore the possibility of EPC in peripheral blood repaired vascular in patients with different extent OSA. Methods 90 adult patients with OSA, 30 healthy controls with matched age, gender were enrolled for this study. The subjects performed Polysomnography, and were divided into four groups based on Apnea Hypopnea Index (AHI). they are mild OSA group, moderate OSA group, severe OSA group and control group respectively, and including 30 patients in each group. Measuring the serum levels of HIF-1?、SDF-1? and VEGF by ELISA. Mononuclear cells were isolated from peripheral blood with density gradient centrifugation, and based on ALDH activity and CD133, CD34, KDR appropriate cell surface markers by flow cytometry (FACS ) to detected the levels of CD133+ EPC、CD133+CD34+ EPC、CD34+ EPC and ALDHloCD34+ EPC. Results The levels of CD133+ EPC、CD133+CD34+ EPC、CD34+ EPC of patients with OSA were increased compared to those in healthy controls (79.08±12.52、31.91±8.89、86.09±17.03, 97.34±16.18、45.19±18.23、123.40±32.73, 119.20±45.50、76.65±31.91、239.40±87.23 vs 51.90±18.85、18.71±8.50、53.29±18.78), but the levels of ALDHlo EPC in mild and moderate OSA groups were increased than those in the controls, and the levels of ALDHlo EPC were significantly decreased in severe OSA group (37.69±11.16、29.52±11.15、13.01± 6.36 vs 20.45± 8.99). Serum levels of HIF-1?、VEGF in patients with OSA were significantly increased compared to those in healthy controls (1.70±0.15、53.29±6.57,1.87±0.35、98.00±7.00,2.56±0.26、155.60±12.80 vs 1.30±0.21、36.79±5.59) but serum levels of SDF-1? were significantly decreased(1971.00±275.50、1587.00±241.70、1180.00±313.20 vs 2173.00±316.50) (P<0.05). Conclusion With increasing severity of OSA , Endothelial progenitor cells (EPCs) levels of mobilization and recruitment have increased, and ALDHlo EPC with vascular repair capacity were decreased, which results in endothelial damage, and increased the risk of cardiovascular disease.

Key words: [Key words] obstructive sleep apnea, HIF-1?, SDF-1?, VEGF, intermittent hypoxia, endothelial progenitor cells (EPCs), acetaldehyde dehydrogenase