急性肺障害における血管内皮前駆細胞の動態解析:自家移植による再生治療の試み

目的：在重症监护病房（ICU）中，纤维蛋白溶解受损与多器官功能障碍和死亡率的高发生率相关。纤溶酶原激活物抑制剂(PAI)-1是纤维蛋白溶解的主要抑制剂。研究PAI-1基因4G/5G多态性（rs1799768）对危重患者血浆PAI-1水平及转归的影响。方法：对41例连续入住ICU的患者进行PAI-1基因多态性评估，测定血浆PAI-1和动脉乳酸浓度，并记录临床严重程度评分。结果：4G等位基因的纯合子血浆PAI-1抗原水平较高。4G/4G基因型平均8 SD PAI-1抗原水平为193.318 167.93 ng/ml， 4G/5G基因型为100.67 8 114.16 ng/ml， 5G/5G基因型为0.43 8 0.53 ng/ml。血浆PAI-1与动脉乳酸浓度以及PAI-1与严重程度评分之间存在显著相关性。4G/4G、4G/5G和5G/5G基因型患者的死亡率分别为63%、33%和0%。结论：上述结果表明PAI-1基因4G/5G多态性影响血浆PAI-1浓度，可损害纤维蛋白溶解，导致器官衰竭，因此4G等位基因的存在增加了死亡风险。

Objective : Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit(ICU). Plasminogen activator inhibitor(PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism(rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients. Methods : In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded. Results : Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean 8 SD PAI-1 antigen level was 193.318 167.93 ng/ml for the 4G/4G genotype, 100.67 8 114.16 ng/ml for the 4G/5G genotype and 0.43 8 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively. Conclusions : These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death.