Bradley J D, Zanaboni P B, Webster R O, Baudendistel L J, Dahms T E
Department of Anesthesiology, St. Louis University School of Medicine, Missouri 63110.
J Appl Physiol (1985). 1991 Nov;71(5):1949-55. doi: 10.1152/jappl.1991.71.5.1949.
The objective of this study was to determine whether adenosine (ADO) prevents phorbol myristate acetate- (PMA) induced lung injury by modulating peptidoleukotrienes (LT) and/or tumor necrosis factor (TNF) production. PMA significantly increased pulmonary vascular resistance (PVR, 275 +/- 4 to 447 +/- 30 cmH2O.1-1.min) and microvascular filtration coefficient.(Kf, 0.024 +/- 0.002 to 0.040 +/- 0.006 g.min-1.cmH2O-1) in isolated blood-perfused rabbit lungs. ADO (5 mumol/min) blocked the increases in PVR (257 +/- 9 to 283 +/- 26) and Kf (0.028 +/- 0.005 to 0.018 +/- 0.002). After PMA (30 min), perfusate levels of LTC4 + LTD4 increased by 15.3 +/- 2.1 pg/ml; LTE4 increased by 15.1 +/- 4.1 pg/ml. ADO reduced the increase in LTC4 + LTD4 to 2.7 +/- 6.1 pg/ml, but total LT increased by 31.9 +/- 16.6 pg/ml, implying that ADO enhanced the conversion of LTC4 and LTD4 to LTE4. MK-886 (L663,536), an LT synthesis inhibitor, blocked the increase in total LT (6.1 +/- 13.9 pg/ml) but did not reduce the PMA-induced increase in Kf (0.022 +/- 0.003 to 0.035 +/- 0.005) or PVR (238 +/- 11 to 495 +/- 21). After PMA administration, perfusate TNF levels were not different from the 10-fold increase observed in control experiments and were not reduced by ADO or MK-886. TNF production was independent of perfusate blood components and presumably due to low levels of endotoxin in the perfusate (70-90 ng/ml). These results indicate that ADO does not protect against PMA-induced acute lung injury by altering circulating levels of LT or TNF.
本研究的目的是确定腺苷（ADO）是否通过调节肽白三烯（LT）和/或肿瘤坏死因子（TNF）的产生来预防佛波酯（PMA）诱导的肺损伤。PMA显著增加了离体血液灌注兔肺的肺血管阻力（PVR，从275±4增至447±30 cmH2O·1-1·min）和微血管滤过系数（Kf，从0.024±0.002增至0.040±0.006 g·min-1·cmH2O-1）。ADO（5 μmol/min）可阻止PVR（从257±9增至283±26）和Kf（从0.028±0.005降至0.018±0.002）的升高。给予PMA（30分钟）后，灌流液中LTC4 + LTD4的水平升高了15.3±2.1 pg/ml；LTE4升高了15.1±4.1 pg/ml。ADO将LTC4 + LTD4的升高幅度降至2.7±6.1 pg/ml，但总LT升高了31.9±16.6 pg/ml，这意味着ADO增强了LTC4和LTD4向LTE4的转化。LT合成抑制剂MK-886（L663,536）可阻止总LT的升高（6.1±13.9 pg/ml），但并未降低PMA诱导的Kf升高（从0.022±0.003增至0.035±0.005）或PVR升高（从238±11增至495±21）。给予PMA后，灌流液中的TNF水平与对照实验中观察到的升高10倍的情况无异，且未被ADO或MK-886降低。TNF的产生与灌流液中的血液成分无关，可能是由于灌流液中内毒素水平较低（70 - 90 ng/ml）。这些结果表明，ADO不能通过改变循环中的LT或TNF水平来预防PMA诱导的急性肺损伤。
