Olson J W, Gebb S A, Orlinska U, Gillespie M N
University of Kentucky, A.B. Chandler Medical Center, College of Pharmacy, Division of Pharmacology and Toxicology, Lexington 40536.
Toxicology. 1989 May 15;55(3):317-26. doi: 10.1016/0300-483x(89)90021-8.
The diamine, putrescine, and polyamines, spermidine and spermine, are low molecular weight organic cations with documented regulatory roles in cell growth and differentiation. Multiple lines of direct and indirect evidence suggest that these organic cations also may function in stimulus-response coupling processes regulating cellular injury and repair. For example, recent studies in monocrotaline-treated rats, hyperoxic rats, and in cultured pulmonary endothelial cells suggest that polyamines regulate pulmonary endothelial integrity and may thus participate in development and/or regression of acute edematous lung injury. To determine if the polyamines are involved in a well-characterized animal model of acute lung injury, the present experiments assessed the relation between changes in polyamine synthesis and development of edema in lungs from rats treated with alpha-naphthylthiourea (ANTU). ANTU caused dose- and time-dependent increases in the lung activity of the initial and rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC) and in the lung contents of the polyamines putrescine, spermidine, and spermine. ANTU also caused dose- and time-dependent increases in the lung wet-to-dry weight ratio indicative of pulmonary edema formation. Changes in lung polyamine biosyntheic activity after ANTU did not relate temporally to changes in the lung wet-to-dry weight ratio: ODC activity was depressed during the 3-h period immediately following ANTU administration, a period when the wet-to-dry weight ratio was increasing, and markedly elevated at 18 h after ANTU administration when the wet-to-dry weight ratio had returned to control levels. Pretreatment of the animals with alpha-difluoromethylornithine, a highly specific inhibitor of ODC, failed to attenuate ANTU-induced increases in lung wet-to-dry weight ratio. These observations indicate polyamine synthesis is enhanced in rat lungs with ANTU-induced pulmonary edema but, unlike certain other models of lung injury and pulmonary edema, accumulation of polyamines probably is not essential for development of edematous lung injury. It is conceivable that in this animal model polyamines play a role in lung repair processes or some longer-term consequence of lung injury.
二胺、腐胺以及多胺（亚精胺和精胺）是低分子量有机阳离子，在细胞生长和分化中具有已被证实的调节作用。多方面的直接和间接证据表明，这些有机阳离子也可能在调节细胞损伤和修复的刺激-反应偶联过程中发挥作用。例如，最近对用野百合碱处理的大鼠、高氧大鼠以及培养的肺内皮细胞的研究表明，多胺调节肺内皮完整性，因此可能参与急性肺水肿性肺损伤的发生和/或消退。为了确定多胺是否参与一种已被充分表征的急性肺损伤动物模型，本实验评估了用α-萘基硫脲（ANTU）处理的大鼠肺中多胺合成变化与肺水肿发展之间的关系。ANTU导致多胺生物合成中初始和限速酶鸟氨酸脱羧酶（ODC）的肺活性以及多胺腐胺、亚精胺和精胺的肺含量呈剂量和时间依赖性增加。ANTU还导致肺湿重与干重比呈剂量和时间依赖性增加，这表明肺水肿形成。ANTU处理后肺多胺生物合成活性的变化与肺湿重与干重比的变化在时间上不相关：在ANTU给药后的3小时内，ODC活性降低，而此时湿重与干重比正在增加；在ANTU给药后18小时，当湿重与干重比已恢复到对照水平时，ODC活性显著升高。用ODC的高度特异性抑制剂α-二氟甲基鸟氨酸对动物进行预处理，未能减弱ANTU诱导的肺湿重与干重比增加。这些观察结果表明，在ANTU诱导的肺水肿大鼠肺中多胺合成增强，但与某些其他肺损伤和肺水肿模型不同，多胺的积累可能不是肺水肿性肺损伤发生所必需的。可以设想，在这个动物模型中，多胺在肺修复过程或肺损伤的某些长期后果中起作用。
