Borawski Jacek, Naumnik Beata, Myśliwiec Michał
Department of Nephrology and Internal Medicine, Medical University, Białystok, Poland.
Kidney Int. 2003 Dec;64(6):2229-37. doi: 10.1046/j.1523-1755.2003.00307.x.
Hepatocyte growth factor (HGF), activin A, and follistatin compose an organotrophic system that may be modulated by heparin. We prospectively studied the effects of unfractionated heparin (UFH) versus low-molecular-weight heparin (LMWH) enoxaparin-anticoagulated hemodialysis on plasma levels of the cytokines.
The factors were measured by immunoassays in 25 chronic hemodialysis patients at the start and at 10 and 180 minutes of the hemodialysis procedure anticoagulated with bolus enoxaparin. Then, the patients were randomized to either receive a bolus and infusion of UFH or to continue LMWH, and were reexamined after 12 weeks.
Predialysis HGF and follistatin were increased (both P < 0.0001), while activin A was normal in hemodialysis patients. Baseline HGF directly correlated with activin A in hemodialysis subjects (P=0.004). In healthy controls, it was positively associated with follistatin (P=0.001). Both HGF and activin A were markedly increased at each interval of enoxaparin-anticoagulated hemodialysis, and follistatin was increased at 10 minutes (all P < 0.0001). The early increments in HGF and follistatin directly depended on the dose of enoxaparin (both P < 0.030). Remarkably, the rise in activin A was inversely associated with the predialysis level of the cytokine (P < 0.0001). The actions of UFH resembled those of LMWH, although the releasing effects on the growth factors were not dose-dependent. The switch from LMWH to UFH resulted in a significant increase in over-dialysis HGF, a fall in follistatin, and no change in activin A.
HGF/activin A/follistatin system is activated and disturbed in chronic hemodialysis patients, including depletion of tissue stores of activin A. Type and dose of heparin used during hemodialysis procedures profoundly influence this pleiotropic system, and may thus modulate vital body functions and course of critical diseases.
肝细胞生长因子（HGF）、激活素A和卵泡抑素构成一个可能受肝素调节的器官营养系统。我们前瞻性地研究了普通肝素（UFH）与低分子肝素（LMWH）依诺肝素抗凝血液透析对细胞因子血浆水平的影响。
通过免疫测定法在25例慢性血液透析患者血液透析开始时、用推注依诺肝素抗凝的血液透析过程10分钟和180分钟时测定这些因子。然后，将患者随机分为接受推注和输注UFH组或继续使用LMWH组，并在12周后重新检查。
血液透析患者透析前HGF和卵泡抑素升高（均P < 0.0001），而激活素A正常。血液透析受试者中基线HGF与激活素A直接相关（P = 0.004）。在健康对照中，它与卵泡抑素呈正相关（P = 0.001）。在依诺肝素抗凝血液透析的每个时间段，HGF和激活素A均显著升高，卵泡抑素在10分钟时升高（均P < 0.0001）。HGF和卵泡抑素的早期升高直接取决于依诺肝素的剂量（均P < 0.030）。值得注意的是，激活素A的升高与细胞因子的透析前水平呈负相关（P < 0.0001）。UFH的作用与LMWH相似，尽管对生长因子的释放作用不依赖于剂量。从LMWH转换为UFH导致透析后HGF显著增加，卵泡抑素下降，激活素A无变化。
慢性血液透析患者中HGF/激活素A/卵泡抑素系统被激活并受到干扰，包括激活素A的组织储存耗竭。血液透析过程中使用的肝素类型和剂量深刻影响这个多效系统，从而可能调节重要身体功能和危重病病程。
