Wang Chun-ping, Han Jun, Ma Xue-mei, Dong Kun, Xiang Yi, Su Shu-hui, Feng Yong-yi, Yang Yong-ping
Department of No. 9 Internal Medicine, Hospital No. 302 of Chinese People's liberation Army, Beijing 100039, China.
Zhonghua Yi Xue Za Zhi. 2005 Dec 14;85(47):3337-41.
To investigate the influence of platelet activating factor (PAF) and its antagonist BN52021 on portal hypertension associated with liver cirrhosis.
Ten SD rats were injected intraperitoneally with carbon tetrachloride to establish a liver cirrhosis model and 10 rats were injected with olive oil as controls. The concentrations of PAF in the blood and liver was examined by rapid (3)H-PAF scintillation proximity assay and the hepatic PAF binding capacity was examined by receptor saturation binding technique. The pressure of portal vein and pressure of femoral artery were measured by intubation method. BN52021 was infused into the portal vein to observe its influence on the blood pressure.
The hepatic PAF levels of the cirrhotic rats was 4.0 ng/g +/- 0.4 ng/g, significantly higher than that of the control rats (2.7 ng/g +/- 0.5 ng/g, P < 0.01). The hepatic efflux PAF level of the cirrhotic rats was 6.3 ng/g +/- 0.6 ng/g, significantly higher than that of the control rats (3.4 ng/g +/- 0.6 ng/g, P < 0.01). The hepatic output PAF levels of the cirrhotic rats was 1.0 ng/g +/- 0.6 ng/g, significantly lower than that of the control rats (0.3 ng/g +/- 0.5 ng/g, P < 0.01). The maximum PAF binding capacity of the cirrhotic rats was 2.8 +/- 0.21 fmol/microg protein, significantly higher than that of the control rats (0.9 +/- 0.06 fmol/microg protein, P < 0.01). However, the receptor affinity was not significantly different between these 2 groups. The portal pressure of the cirrhotic rats was 12.2 mm Hg +/- 0.7 mm Hg, significantly higher than that of the control rats (5.3 mm Hg +/- 0.6 mm Hg, P < 0.01). The femoral arterial pressure of the cirrhotic rats was 82 mm Hg +/- 10 mm Hg, significantly lower than that of the control rats (114 mm Hg +/- 9 mm Hg, P < 0.01). Infusion of PAF via the portal vein increased the portal pressure from 12.1 mm Hg +/- 0.6 mm Hg with an increase of 32% (P < 0.01) in the cirrhotic rats, and from 7.7 mm Hg +/- 0.8 mm Hg with an increase of 23%. The PAF response of the cirrhotic rats was 4.1 mm Hg +/- 1.0 mm Hg (227%), significantly higher than that of the control rats (1.8 mm Hg +/- 0.3 mm Hg, P < 0.01). The femoral artery pressure decreased from 82 mm Hg +/- 10 mm Hg to 48 mm Hg +/- 4 mm Hg (P < 0.01) in the cirrhotic rats, and from 114 mm Hg +/- 9 mm Hg to 52 mm Hg +/- 4 mm Hg (P < 0.01). After portal infusion of BN52021 the portal pressure decreased from 14.6 mm Hg +/- 1.6 mm Hg to 12.3 mm Hg +/- 0.8 mm Hg (P < 0.05) with a decrease of 16%, however, did not significantly influenced the femoral arterial pressure in the cirrhotic rats, and did not significantly influenced the portal pressure and femoral arterial pressure in the control rats.
The increased hepatic PAF synthesis in cirrhotic is the major source of elevated circulating PAF It upregulates the hepatic hemodynamics that contributes to portal hypertension. The increased portal pressure by endogenous PAF can be decreased to a certain extent by BN52021 which may be used in treatment of portal hypertension.
探讨血小板活化因子（PAF）及其拮抗剂BN52021对肝硬化门静脉高压的影响。
将10只SD大鼠腹腔注射四氯化碳建立肝硬化模型，另10只大鼠注射橄榄油作为对照。采用快速（3）H-PAF闪烁邻近分析法检测血液和肝脏中PAF的浓度，采用受体饱和结合技术检测肝脏PAF结合能力。通过插管法测量门静脉压力和股动脉压力。向门静脉内注入BN52021，观察其对血压的影响。
肝硬化大鼠肝脏PAF水平为4.0 ng/g±0.4 ng/g，显著高于对照组大鼠（2.7 ng/g±0.5 ng/g，P<0.01）。肝硬化大鼠肝脏流出PAF水平为6.3 ng/g±0.6 ng/g，显著高于对照组大鼠（3.4 ng/g±0.6 ng/g，P<0.01）。肝硬化大鼠肝脏输出PAF水平为1.0 ng/g±0.6 ng/g，显著低于对照组大鼠（0.3 ng/g±0.5 ng/g，P<0.01）。肝硬化大鼠PAF最大结合能力为2.8±0.21 fmol/μg蛋白，显著高于对照组大鼠（0.9±0.06 fmol/μg蛋白，P<0.01）。然而，两组之间受体亲和力无显著差异。肝硬化大鼠门静脉压力为12.2 mmHg±0.7 mmHg，显著高于对照组大鼠（5.3 mmHg±0.6 mmHg，P<0.01）。肝硬化大鼠股动脉压力为82 mmHg±10 mmHg，显著低于对照组大鼠（114 mmHg±9 mmHg，P<0.01）。经门静脉注入PAF后，肝硬化大鼠门静脉压力从12.1 mmHg±0.6 mmHg升高至16.0 mmHg±0.6 mmHg，升高了32%（P<0.01），对照组大鼠门静脉压力从7.7 mmHg±0.8 mmHg升高至9.4 mmHg±0.8 mmHg，升高了23%。肝硬化大鼠PAF反应为4.1 mmHg±1.0 mmHg（227%），显著高于对照组大鼠（1.8 mmHg±0.3 mmHg，P<0.01）。肝硬化大鼠股动脉压力从82 mmHg±10 mmHg降至48 mmHg±4 mmHg（P<0.01），对照组大鼠股动脉压力从114 mmHg±9 mmHg降至52 mmHg±4 mmHg（P<0.01）。门静脉注入BN52021后，肝硬化大鼠门静脉压力从14.6 mmHg±1.6 mmHg降至12.3 mmHg±0.8 mmHg（P<0.05），降低了16%，但对肝硬化大鼠股动脉压力无显著影响，对对照组大鼠门静脉压力和股动脉压力也无显著影响。
肝硬化时肝脏PAF合成增加是循环中PAF升高的主要来源，它上调肝脏血流动力学，导致门静脉高压。内源性PAF引起的门静脉压力升高可被BN52021在一定程度上降低，BN52021可能用于治疗门静脉高压。
