储存的浓缩红细胞中的血浆和脂质在动物模型中会导致急性肺损伤。
Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.
作者信息
Silliman C C, Voelkel N F, Allard J D, Elzi D J, Tuder R M, Johnson J L, Ambruso D R
机构信息
Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80220, USA.
出版信息
J Clin Invest. 1998 Apr 1;101(7):1458-67. doi: 10.1172/JCI1841.
Transfusion-related acute lung injury (TRALI) is a serious complication of hemotherapy. During blood storage, lipids are generated and released into the plasma. In this study, the role of these lipids in TRALI was investigated using an isolated, perfused rat lung model. Rats were pretreated with endotoxin (LPS) or saline in vivo and the lungs were isolated, ventilated, and perfused with saline, or (a) 5% (vol/ vol) fresh human plasma, (b) plasma from stored blood from the day of isolation (D.0) or from the day of outdate (D.42), (c) lipid extracts from D.42 plasma, or (d) purified lysophosphatidylcholines. Lungs from saline or LPS-pretreated rats perfused with fresh (D.0) plasma showed no pulmonary damage as compared with saline perfused controls. LPS pretreatment/D.42 plasma perfusion caused acute lung injury (ALI) manifested by dramatic changes in both pulmonary artery pressure and edema. Incubation of LPS pre-tx rats with mibefradil, a Ca2+ channel blocker, or WEB 2170, a platelet-activating factor (PAF) receptor antagonist, inhibited ALI caused by D.42 plasma. Lung histology showed neutrophil sequestration without ALI with LPS pretreatment/saline or D.0 plasma perfusion, but ALI with LPS pretreatment/D.42 plasma perfusion, and inhibition of D.42 plasma induced ALI with WEB 2170 or mibefradil. A significant increase in leukotriene E4 was present in LPS-pretreated/D.42 plasma-perfused lungs that was inhibited by WEB 2170. Lastly, significant pulmonary edema was produced when lipid extracts of D.42 plasma or lysophosphatidylcholines were perfused into LPS-pretreated lungs. Lipids caused ALI without vasoconstriction, except at the highest dose employed. In conclusion, both plasma and lipids from stored blood produced pulmonary damage in a model of acute lung injury. TRALI, like the adult respiratory distress syndrome, may be the result of two insults: one derived from stored blood and the other from the clinical condition of the patient.
输血相关急性肺损伤（TRALI）是血液治疗的一种严重并发症。在血液储存过程中，脂质生成并释放到血浆中。在本研究中，使用离体灌注大鼠肺模型研究了这些脂质在TRALI中的作用。大鼠在体内用内毒素（LPS）或生理盐水预处理，然后分离肺，进行通气，并灌注生理盐水，或（a）5%（体积/体积）新鲜人血浆、（b）分离日（D.0）或过期日（D.42）储存血液的血浆、（c）D.42血浆的脂质提取物或（d）纯化的溶血磷脂酰胆碱。与灌注生理盐水的对照组相比，用新鲜（D.0）血浆灌注的生理盐水或LPS预处理大鼠的肺未显示出肺损伤。LPS预处理/D.42血浆灌注导致急性肺损伤（ALI），表现为肺动脉压和水肿的显著变化。用钙通道阻滞剂米贝拉地尔或血小板活化因子（PAF）受体拮抗剂WEB 2170孵育LPS预处理大鼠，可抑制D.42血浆引起的ALI。肺组织学显示，LPS预处理/生理盐水或D.0血浆灌注时，有中性粒细胞滞留但无ALI，但LPS预处理/D.42血浆灌注时有ALI，且WEB 2170或米贝拉地尔可抑制D.42血浆诱导的ALI。LPS预处理/D.42血浆灌注的肺中白三烯E4显著增加，而WEB 2170可抑制这种增加。最后，当将D.42血浆的脂质提取物或溶血磷脂酰胆碱灌注到LPS预处理的肺中时，会产生显著的肺水肿。脂质导致ALI但无血管收缩，最高剂量时除外。总之，储存血液中的血浆和脂质在急性肺损伤模型中均造成了肺损伤。TRALI与成人呼吸窘迫综合征一样，可能是两种损伤的结果：一种来自储存血液，另一种来自患者的临床状况。
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