Block E R
Research Service, Veterans Administration Medical Center, Gainesville, Florida 32602.
Exp Lung Res. 1988;14 Suppl:937-58. doi: 10.3109/01902148809064185.
Because high partial pressures of oxygen (O2) can cause peroxidative cleavage of membrane lipids, it is plausible to hypothesize that hyperoxia alters the physical state and composition of lipids in the membranes of pulmonary endothelial cells and that manipulation of the lipid profile may modify endothelial cell tolerance to hyperoxic injury. To test this, porcine pulmonary artery endothelial cells were exposed to 95% O2 at 1 atmosphere absolute (ATA) in the presence or absence of cis vaccenic acid (CVA), a monounsaturated fatty acid (C18:1#11). Plasma membrane fluidity was assessed by fluorescence spectroscopy, plasma membrane lipid composition was quantitated using thin layer and gas chromatography, and cytotoxicity was monitored by measuring release of lactate dehydrogenase (LDH). Hyperoxia caused peroxidation of membrane lipids and decreased fluidity in three distinct lipid domains within the plasma membrane. Incubation with CVA was associated with a reduction in the degree of unsaturation of the constituent fatty acids within all plasma membrane lipid subclasses except monoglycerides. CVA-treated cells were also more resistant to hyperoxic injury as judged by LDH release. These results support the hypothesis that cells with membranes in which the fatty acyl chains are more resistant to the disordering effects of high O2 tensions may be more resistant to O2 toxicity.
由于高氧分压（O2）可导致膜脂质的过氧化裂解，因此可以合理推测，高氧会改变肺内皮细胞膜脂质的物理状态和组成，并且脂质分布的改变可能会改变内皮细胞对高氧损伤的耐受性。为了验证这一点，将猪肺动脉内皮细胞置于1个绝对大气压（ATA）的95% O2环境中，同时存在或不存在顺式vaccenic酸（CVA，一种单不饱和脂肪酸（C18:1#11））。通过荧光光谱法评估质膜流动性，使用薄层色谱法和气相色谱法定量质膜脂质组成，并通过测量乳酸脱氢酶（LDH）的释放来监测细胞毒性。高氧导致膜脂质过氧化，并降低了质膜内三个不同脂质结构域的流动性。与CVA孵育会导致除甘油单酯外的所有质膜脂质亚类中组成脂肪酸的不饱和度降低。通过LDH释放判断，经CVA处理的细胞对高氧损伤也更具抗性。这些结果支持了这样的假设，即细胞膜中脂肪酰链对高氧张力的无序化作用更具抗性的细胞可能对氧毒性更具抗性。
