Olson J W, Hacker A D, Altiere R J, Gillespie M N
Am J Physiol. 1984 Oct;247(4 Pt 2):H682-5. doi: 10.1152/ajpheart.1984.247.4.H682.
Previous work in our laboratory has shown that the development of monocrotaline-induced pulmonary vascular disease in rats is preceded by a prolonged activation of lung ornithine decarboxylase (ODC). We now report that significant increases in rat lung adenosylmethionine decarboxylase activity and levels of the diamine putrescine and the polyamines, spermidine and spermine, are produced by a single dose of monocrotaline (MCT). Lung putrescine levels were increased from days 7 through 21, and both spermidine and spermine were first elevated at day 10 following MCT administration. This sustained elevation of lung polyamine levels substantially preceded the development of right ventricular hypertrophy and pulmonary hypertension, which were first evident at days 14 and 16, respectively. Continuous treatment with alpha-difluoromethylornithine, a highly specific enzyme-activated, irreversible inhibitor of ODC activity, prevented the development of MCT-induced pulmonary toxicity. It thus appears that ODC and the polyamines may be important mediators of hypertensive pulmonary vascular disease that develops in response to monocrotaline administration.
我们实验室之前的研究表明，在大鼠中，单剂量的野百合碱（MCT）会导致肺鸟氨酸脱羧酶（ODC）长期激活，随后引发野百合碱诱导的肺血管疾病。我们现在报告，单剂量的野百合碱（MCT）会使大鼠肺腺苷甲硫氨酸脱羧酶活性以及二胺腐胺、多胺亚精胺和精胺的水平显著升高。肺腐胺水平在第7天至第21天升高，MCT给药后第10天，亚精胺和精胺均首次升高。肺多胺水平的持续升高在右心室肥大和肺动脉高压出现之前就已大幅出现，右心室肥大和肺动脉高压分别在第14天和第16天首次明显出现。用α-二氟甲基鸟氨酸持续治疗，α-二氟甲基鸟氨酸是一种高度特异性的酶激活、不可逆的ODC活性抑制剂，可预防MCT诱导的肺毒性的发展。因此，ODC和多胺可能是因给予野百合碱而引发的高血压性肺血管疾病的重要介质。
