Lin H I, Hsu K, Yan H C, Shen C Y
Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan R.O.C.
J Formos Med Assoc. 1990 Sep;89(9):742-8.
The pathogenesis of adult respiratory distress syndrome (ARDS) is not clear, and its therapy is still a problem. Pentoxifylline, a methylxanthine derivative, can inhibit phosphodiesterase activity and thus increase the intracellular cAMP. There are also some hypotheses that pentoxifylline can attenuate pulmonary edema. In order to evaluate the protective effect of pentoxifylline in acute lung injury, we set up an isolated lung perfusion model in rats and induced experimental acute lung injury similar to ARDS by intravenously infused phorbol myristate acetate (PMA) 7.5 micrograms/300 g body weight. Four groups of experimental rats were studied: group 1, normal control group, neither PMA nor pentoxifylline was used in 6 rats; group 2 (acute lung injury group), only PMA was infused in 8 rats; group 3 (protective group), pentoxifylline 100 mg/300 g body weight was given intravenously before PMA infusion in 6 rats; group 4, only pentoxifylline was given in 6 rats. Pulmonary arterial pressure (PAP) as well as lung weight changes were recorded before and 5, 10, 15, 20 and 25 minutes after drug injection. Bronchial lavage fluids were then measured for albumin concentration. We found that PAP was strikingly increased in group 2 (54.0 +/- 8.8 mmHg), but the increase was significantly reduced in group 3 (29.8 +/- 5.8 mmHg, p less than 0.001). Similarly, the lung weight gain was markedly increased in group 2 (4.69 +/- 1.28 g), but was significantly attenuated in group 3 (1.25 +/- 1.60 g, p less than 0.001). There was no apparent change in PAP and lung weight gain throughout the entire procedure in groups 1 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)
成人呼吸窘迫综合征（ARDS）的发病机制尚不清楚，其治疗仍是一个难题。己酮可可碱是一种甲基黄嘌呤衍生物，可抑制磷酸二酯酶活性，从而增加细胞内的环磷酸腺苷（cAMP）。也有一些假说认为己酮可可碱可减轻肺水肿。为了评估己酮可可碱在急性肺损伤中的保护作用，我们建立了大鼠离体肺灌注模型，并通过静脉注射7.5微克/300克体重的佛波醇肉豆蔻酸酯（PMA）诱导出类似于ARDS的实验性急性肺损伤。研究了四组实验大鼠：第1组为正常对照组，6只大鼠既未使用PMA也未使用己酮可可碱；第2组（急性肺损伤组），8只大鼠仅注入PMA；第3组（保护组），6只大鼠在注入PMA前静脉给予100毫克/300克体重的己酮可可碱；第4组，6只大鼠仅给予己酮可可碱。记录药物注射前及注射后5、10、15、20和25分钟时的肺动脉压（PAP）以及肺重量变化。然后测定支气管灌洗液中的白蛋白浓度。我们发现第2组的PAP显著升高（54.0±8.8毫米汞柱），但第3组的升高明显降低（29.8±5.8毫米汞柱，p<0.001）。同样，第2组的肺重量增加显著升高（4.69±1.28克），但第3组明显减轻（1.25±1.60克，p<0.001）。第1组和第4组在整个过程中PAP和肺重量增加均无明显变化。（摘要截短于250字）
