摘要
AIM： To develop a pharmacodynamic model of porta hypertension from chronic hepatitis. METHODS： Pathological changes and collagen depositions were analyzed using morphometry to confirm CCI4-induced chronic hepatitis. At do, d28, ds6 and d84 of the process, the portal perfused velocities （μL/min） in isolated rat livers were exactly controlled with a quanti-fied pump. The pressure （mmHg） was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume （300 mL） of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetyl- choline were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.CONCLUSION： A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concen- trations of phenylephrine and acetylcholine.
AIM:To develop a pharmacodynamic model of portal hypertension from chronic hepatitis.METHODS:Pathological changes and collagen depositions were analyzed using morphometry to confirm CCl 4-induced chronic hepatitis.At d 0,d 28,d 56 and d 84 of the process,the portal perfused velocities (μL/min) in isolated rat livers were exactly controlled with a quantified pump.The pressure (mmHg) was monitored with a Physiological System.The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume (300 mL) of the circulating perfusate.The equation,the median effective concentration and its 95% confidence intervals of phenylephrine or acetylcholine were regressed with Prism-4 software in nonlinear fit and various slopes.In the isolated perfused rat livers with chronic hepatitis,both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.RESULTS:At d 0,d 28,d 56 and d 84,the equations of portal pressure potency from the concentrations of phenylephrine used to constrict the portal vein in isolated perfused rat livers were Y=0.1732 + 0.3970/[1 + 10 (-4.3061-0.4407 X) ],Y=-0.004934 + 0.12113/[1 + 10 (-3.1247-0.3262 X) ],Y=0.0104 + 0.2643/[1 + 10 (-8.8462-0.9579 X) ],and Y=0.01603 + 0.12107/[1 + 10 (-5.1134-0.563 X) ];the median effective concentrations were 1.69 × 10-10 mol/L,2.64 × 10-10 mol/L,5.82 × 10-10 mol/L,and 8.24 × 10-10 mol/L,respectively.The equations from the concentrations of acetylcholine used to relax the portal vein were Y =-0.4548 + 0.3274/[1 + 10 (6.1538 + 0.5554 X) ],Y=-0.05391 + 0.06424/[1 + 10 (3.8541 + 0.3469 X) ],Y=-0.2733 + 0.22978/[1 + 10 (3.0472 + 0.3008 X) ],and Y=-0.0559 + 0.053178/[1 + 10 (5.6336 + 0.5883 X) ];the median effective concentrations were 8.40 × 10-10 mol/L,7.73 × 10-12 mol/L,5.98 × 10-11 mol/L,and 2.66 × 10-10 mol/L,respectively.CONCLUSION:A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concentrations of phenylephrine and acetylcholine.
基金
Supported by The Major State Creative New Drug Project,No.2009ZX09502-017
Education Ministry Science Foundation ofChina,No. 108019
