Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF.
Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF.
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腺苷可防止兔肺中的佛波酯损伤：白三烯和 TNF 的作用。
DOI：
10.1152/jappl.1991.71.5.1949
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Dahms,TE
中科院分区：
文献类型：
--
作者：
Bradley,JD;Zanaboni,PB;Webster,RO;Baudendistel,LJ;Dahms,TE
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) 的产生来预防佛波醇肉豆蔻酸酯乙酸酯 (PMA) 诱导的肺损伤。 PMA 显着增加离体血液灌注兔肺中的肺血管阻力（PVR，275 +/- 4 至 447 +/- 30 cmH2O.1–1.min）和微血管滤过系数（Kf，0.024 +/- 0.002 至 0.040 +/- 0.006 g.min-1.cmH2O-1）。 ADO (5 μmol/min) 阻止 PVR (257 +/- 9 至 283 +/- 26) 和 Kf (0.028 +/- 0.005 至 0.018 +/- 0.002) 的增加。 PMA（30 分钟）后，LTC4 + LTD4 灌流液水平增加 15.3 +/- 2.1 pg/ml； LTE4 增加了 15.1 +/- 4.1 pg/ml。 ADO 将 LTC4 + LTD4 的增加减少至 2.7 +/- 6.1 pg/ml，但总 LT 增加了 31.9 +/- 16.6 pg/ml，这意味着 ADO 增强了 LTC4 和 LTD4 向 LTE4 的转化。 MK-886 (L663,536) 是一种 LT 合成抑制剂，可阻止总 LT 的增加（6.1 +/- 13.9 pg/ml），但不会减少 PMA 诱导的 Kf（0.022 +/- 0.003 至 0.035 +/- 0.005）或 PVR（238 +/- 11 至 495 +/- 21）的增加。施用 PMA 后，灌注液 TNF 水平与对照实验中观察到的 10 倍增加没有不同，并且 ADO 或 MK-886 没有降低 TNF 水平。 TNF 的产生与灌注液血液成分无关，可能是由于灌注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 LT 或 TNF 的循环水平来防止 PMA 诱导的急性肺损伤。
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.