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

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

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、ALDHloCD34^+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ALDHloCD34^+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ALDHloCD34^+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。

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 into 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 eentrifugation, and flow cytometry was used to detect levels of CD133＋KDR＋ EPC, CD133＋CD34＋ EPC, CD34＋KDR＋ EPC and ALDH＋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 ALDW＋CD34＋KDW EPC were higher in mild and moderate OSA groups than that of the control groups, and the levels of ALDW＋CD34＋KDR＋EPC were significantly lower in severe OSA group than those of control, mild and moderate OSA groups. Serum levels of HIF-1α. VEGF were significantly higher 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 ALDWCD34＋KDR＋ EPC with vascular repair capacity keeps to invariability, even decreases in patients with severe OSA, which results in endothelial damage, and increases the risk of cardiovascular disease.