Takeoka M, Sakai A, Ueda G, Ge R L, Ishizaki T, Panos R J, Taniguchi S
Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan.
Tohoku J Exp Med. 1997 Dec;183(4):273-84. doi: 10.1620/tjem.183.273.
We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.
我们研究了用二丁酰环磷腺苷（db-cAMP）或环鸟苷酸（cGMP）预处理对内毒素诱导的离体灌注大鼠肺血流动力学变化和肺血管通透性的影响。腹腔注射肠炎沙门氏菌内毒素（2毫克/千克）可导致静脉储器升高后肺动脉阻力（Ra）增加、肺滤过系数（Kf）增加以及肺湿重与干重（W/D）比值增加。用db-cAMP预处理可阻断内毒素诱导的Ra、Kf和W/D比值增加。用cGMP预处理仅减弱了内毒素引起的Ra增加。此外，在内毒素注射2小时后给予db-cAMP可减弱内毒素处理诱导的Ra增加。内毒素引起的Kf和W/D比值增加不受db-cAMP后处理的影响。由于内毒素引起的Ra、Kf和W/D比值增加可被db-cAMP预处理阻断，因此增加细胞内cAMP水平的药物可能有助于预防急性肺血管损伤。
