Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
Clin J Am Soc Nephrol. 2011 Jun;6(6):1345-53. doi: 10.2215/CJN.10911210. Epub 2011 May 19.
Angiogenesis is a key response to tissue ischemia that may be impaired by uremia. Although early-outgrowth endothelial progenitor-like cells promote angiogenesis in the setting of normal renal function, cells from uremic patients are dysfunctional. When compared with conventional hemodialysis, it was hypothesized that nocturnal hemodialysis would improve the in vivo angiogenic activity of these cells in a well described model of ischemic vascular disease.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Early-outgrowth endothelial progenitor-like cells were cultured from healthy controls (n = 5) and age- and gender-matched conventional hemodialysis (12 h/wk, n = 10) and nocturnal hemodialysis (30 to 50 h/wk, n = 9) patients. Cells (5 × 10(5)) or saline were injected into the ischemic hindlimb of athymic nude rats 1 day after left common iliac artery ligation.
Although conventional dialysis cell injection had no effect versus saline, nocturnal hemodialysis and healthy control cell injection significantly improved ischemic hindlimb perfusion and capillary density. Nocturnal hemodialysis cell injection was also associated with significant increases in endogenous angiopoietin 1 expression in the ischemic hindlimb compared with saline and conventional dialysis cell injection.
In contrast to a conventional dialytic regimen, nocturnal hemodialysis is associated with a significantly improved ability of early-outgrowth endothelial progenitor-like cells to promote angiogenesis and thus restore perfusion in a model of ischemic vascular disease.
血管生成是组织缺血的关键反应,可能会被尿毒症所损害。尽管早期生长的内皮祖细胞样细胞在正常肾功能的情况下可以促进血管生成,但是尿毒症患者的细胞功能失调。与常规血液透析相比,本研究假设夜间血液透析可以改善这些细胞在缺血性血管疾病的一个良好描述的模型中的体内血管生成活性。
设计、环境、参与者和测量:从健康对照者(n = 5)和年龄、性别匹配的常规血液透析(每周 12 小时,n = 10)和夜间血液透析(每周 30 到 50 小时,n = 9)患者中培养早期生长的内皮祖细胞样细胞。细胞(5 × 10(5))或生理盐水在左髂总动脉结扎后 1 天注入到去胸腺裸鼠的缺血性后肢。
尽管常规透析细胞注射与生理盐水相比没有效果,但夜间血液透析和健康对照细胞注射明显改善了缺血性后肢的灌注和毛细血管密度。与生理盐水和常规透析细胞注射相比,夜间血液透析细胞注射也与缺血性后肢内源性血管生成素 1 表达的显著增加相关。
与常规透析方案相比,夜间血液透析与早期生长的内皮祖细胞样细胞促进血管生成的能力显著提高有关,从而在缺血性血管疾病模型中恢复灌注。