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Effects of renal cytoprotective agents on erythrocyte membrane stability.

机译:肾细胞保护剂对红细胞膜稳定性的影响。

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摘要

To elucidate potential mechanisms of ischemic renal injury, investigators often use drugs that interfere with specific pathological pathways and study their protective efficacy in in vitro models of ischemia, such as isolated renal proximal tubules subjected to hypoxia. However, the protective effects of certain drugs may depend on non-specific membrane-stabilizing properties. We have studied the effects of several drugs on membrane integrity using osmotic lysis of erythrocytes as a model system. Freshly isolated rabbit erythrocytes were subjected to a hypotonic shock, and the protective effects of various calcium channel blockers, phospholipase inhibitors, free fatty acids, the NO-synthase inhibitor L-NAME, the amino acid glycine and its receptor-analogue strychnine, and two chloride channel blockers were examined. Most agents protected erythrocytes against hypotonic hemolysis when added to the medium in the same concentration range as used in suspensions of hypoxic proximal tubules. Only the protective agents that proposedly act via a blockade of chloride influx (glycine, strychnine and the chloride channel blockers), did not attenuate hypotonic hemolysis. The erythrocyte hemolysis assay may provide an easy and rapid method to screen for non-specific membrane-stabilizing effects of potentially cytoprotective agents.
机译:为了阐明缺血性肾损伤的潜在机制,研究人员经常使用会干扰特定病理途径的药物,并在局部缺血的体外模型中研究其保护作用,例如遭受缺氧的孤立肾近端肾小管。但是,某些药物的保护作用可能取决于非特异性的膜稳定特性。我们使用红细胞的渗透裂解作为模型系统研究了几种药物对膜完整性的影响。对新鲜分离的兔红细胞进行低渗性休克,各种钙通道阻滞剂,磷脂酶抑制剂,游离脂肪酸,NO合酶抑制剂L-NAME,氨基酸甘氨酸及其受体类似物士的宁的保护作用为两种检查了氯通道阻滞剂。当以与缺氧近端小管悬液相同的浓度范围添加到培养基中时,大多数试剂可保护红细胞免受低渗溶血作用。仅建议通过阻断氯离子流入(甘氨酸,士的宁和氯离子通道阻滞剂)起作用的保护剂不能减弱低渗性溶血。红细胞溶血测定法可提供一种简便,快速的方法来筛选潜在细胞保护剂的非特异性膜稳定作用。

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