Cristol J P, Maggi M F, Bosc J Y, Badiou S, Delage M, Vernet M H, Michel F, Castel J, Canaud B, Descomps B
Service de Biochimie A, Hôpital Lapeyronie, Montpellier.
C R Seances Soc Biol Fil. 1997;191(4):603-16.
Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.
心血管疾病是接受血液透析治疗的慢性肾衰竭患者的首要死因。脂质代谢改变和氧化应激被认为是血管危险因素。对它们的纠正可能有助于预防动脉粥样硬化。为了评估一种治疗干预的益处，我们通过测定氧活性物质（ROS）的产生、防御机制水平以及一氧化氮（NO）与ROS之间的平衡（这决定了NO的抗氧化或促氧化作用），分析了血液透析患者的氧化代谢情况。在用纤维素膜（铜仿膜）进行透析过程中，观察到血小板产生的过氧化氢增加（12 - HETE）（5.62±0.94 pg）；同样，单核细胞（荧光指数：115±24）和多形核细胞（荧光指数：115±24）产生的超氧阴离子（O2(0)-）增加。另一方面，抗氧化防御能力显著降低，红细胞超氧化物歧化酶活性（0.92±0.06 U/mg Hg）和红细胞维生素E浓度（0.7±0.07 mg/l）下降。我们已经证明，由于NO合酶抑制剂或激活剂的积累，L - 精氨酸/NO途径发生了深刻改变。在透析过程中减少ROS产生的必要性证明了使用更具生物相容性的膜是合理的，例如改性纤维素膜或合成膜，可减少白细胞活化。此外，NO合成酶抑制剂可通过对流优先清除。最后，补充外源性抗氧化剂，如口服维生素E（500 mg/天，持续6个月）可使红细胞维生素E水平正常化，并同时降低丙二醛浓度。总之，血液透析中观察到的氧化代谢改变是多因素的：预防措施包括使用更具生物相容性的材料、使NO/ROS平衡重新平衡以及补充外源性抗氧化剂。
