Jain S K
J Clin Invest. 1985 Jul;76(1):281-6. doi: 10.1172/JCI111958.
Phospholipid distribution across erythrocyte membrane bilayer is asymmetrical. In normal erythrocytes, entire phosphatidylserine (PS) and most of the phosphatidylethanolamine (PE) is present on the cytoplasmic side of membrane bilayer, whereas phosphatidylcholine (PC) and sphingomyelin (SM) are predominantly present at the outer side of membrane bilayer. The present study was undertaken to determine whether membrane lipid peroxidation has any effect on the distribution of PS, PE, and PC across erythrocyte membrane bilayer in vivo in an animal model. Erythrocyte membrane lipid peroxidation was induced in rats by administering phenylhydrazine, an oxidant drug. Membrane phospholipid organization was determined by using bee venom phospholipase-A2 and indirectly by measuring clotting time on recalcification of normal human platelet-poor plasma in the presence of Russell's viper venom. Phenylhydrazine administration to rats caused significant membrane lipid peroxidation as measured by the accumulation of malonyldialdehyde (MDA), an end product of fatty acid peroxidation, as well as externalization of a significant portion of PS and PE from the inner to the outer side of membrane bilayer in erythrocytes. There was a significant positive correlation (r) between the amount of MDA accumulated in the erythrocytes and the movement of PS (r = 0.92) and PE (r = 0.96) from inner to the outer membrane bilayer and PC (r = 0.81) from outer to the inner membrane bilayer. Erythrocytes of phenylhydrazine-treated rats also showed significantly reduced clotting time. This reduction in clotting time had a significant positive correlation with MDA accumulation (r = 0.92) and PS externalization (r = 0.90). Both the effect of phenylhydrazine on erythrocyte membrane lipid peroxidation and alterations in phospholipid organization and coagulability were blocked when rats were simultaneously administered with vitamin E or C antioxidants.
磷脂在红细胞膜双分子层中的分布是不对称的。在正常红细胞中，整个磷脂酰丝氨酸（PS）和大部分磷脂酰乙醇胺（PE）存在于膜双分子层的细胞质侧，而磷脂酰胆碱（PC）和鞘磷脂（SM）主要存在于膜双分子层的外侧。本研究旨在确定在动物模型中，膜脂质过氧化是否对PS、PE和PC在红细胞膜双分子层中的分布有任何影响。通过给予氧化药物苯肼在大鼠中诱导红细胞膜脂质过氧化。使用蜂毒磷脂酶 - A2并通过在存在罗素蝰蛇毒的情况下测量正常人少血小板血浆再钙化时的凝血时间间接确定膜磷脂组织。给大鼠施用苯肼导致显著的膜脂质过氧化，这通过脂肪酸过氧化终产物丙二醛（MDA）的积累以及红细胞中PS和PE从膜双分子层内侧向外周的大量外化来衡量。红细胞中积累的MDA量与PS（r = 0.92）和PE（r = 0.96）从内膜双分子层向外膜双分子层的移动以及PC（r = 0.81）从外膜双分子层向内膜双分子层的移动之间存在显著正相关。苯肼处理的大鼠的红细胞也显示出凝血时间显著缩短。凝血时间的这种缩短与MDA积累（r = 0.92）和PS外化（r = 0.90）有显著正相关。当大鼠同时给予维生素E或C抗氧化剂时，苯肼对红细胞膜脂质过氧化的影响以及磷脂组织和凝固性的改变均被阻断。
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