Bakhle Y S
Biochem Pharmacol. 1982 Nov 1;31(21):3395-401. doi: 10.1016/0006-2952(82)90617-7.
The effect of pulmonary oedema on the pharmacokinetic function of rat lungs was studied using prostaglandin E2 (PGE2) as substrate; oedema was induced by alpha-naphthyl thiourea (ANTU). Male rats were given a single i.p. injection of ANTU (10 mg/kg). Lung wet weight, dry:wet weight ratio and pleural transudate were measured at fixed times up to 50 hr after treatment. Wet weight was increased after 4 hr and remained higher than controls until 50 hr; dry:wet weight ratios were different only at 6 and 16 hr. Survival of PGE2 (measured by bioassay) was increased at 4 hr, reached a peak value of about six times the control survival at 6 hr and returned to normal by 50 hr. Using 14C-PGE2 as substrate, survival was maximal at 16 hr and back to normal by 50 hr. The efflux profiles of radioactivity showed an increase in T1/2 by 4 hr rising to a maximum at 28 hr and a normal value at 50 hr. Changes in PGE2 survival precede the period of oedema (assessed by dry:wet ratio) and could be used as an early warning of oedematous states. This altered pharmacokinetic function of lung could also have systemic effects.
以前列腺素E2(PGE2)为底物,研究肺水肿对大鼠肺药代动力学功能的影响;用α-萘基硫脲(ANTU)诱导肺水肿。给雄性大鼠腹腔注射一次ANTU(10 mg/kg)。在治疗后长达50小时的固定时间测量肺湿重、干重与湿重之比以及胸腔渗出液。4小时后湿重增加,直至50小时一直高于对照组;干重与湿重之比仅在6小时和16小时时有所不同。PGE2的存留率(通过生物测定法测量)在4小时时增加,在6小时时达到约为对照存留率六倍的峰值,并在50小时时恢复正常。以14C-PGE2为底物时,存留率在16小时时最高,并在50小时时恢复正常。放射性流出曲线显示,半衰期在4小时时增加,在28小时时达到最大值,在50小时时恢复正常。PGE2存留率的变化先于水肿期(通过干重与湿重之比评估),可作为水肿状态的早期预警。肺的这种改变的药代动力学功能也可能产生全身影响。