灌流流速决定慢性肝损伤大鼠的离体门脉压力

Portal pressure determined by perfusion velocity in isolated chronically injured rat liver in vitro

目的:建立灌流流速所决定的慢性各阶段肝损伤大鼠离体门脉压力方程.方法:常规观察CCl4慢性肝损伤第0、28、56、84天的肝脏系数与肝脏病,大鼠肝动脉、门脉和肝静脉插管,经肝动脉冲净残血,门脉灌流状态下游离肝脏;定量蠕动泵调节门脉灌流流速(μL/min),生物机能实验系统监测压力(mmHg),采用Prism-4非线型可变斜率回归由对数流速所决定的压力效能方程式,计算半效对数流速及其95%的可信区间.结果:在连续CCl4慢性肝损伤0、28、56、84天,由灌流数值流速(μL/min)决定的离体大鼠门脉灌流压力(mmHg)效能方程分别为y=-0.1428+1.1423/[1+10(13.805-3.84x)](r2=0.9996)、y=-0.1570+1.419/[1+10(4.666-1.27x)](r2=0.9958)、y=0.05106+0.96594/[1+10(10.877-2.958x)](r2=0.9987)和y=-0.09893+1.406/[1+10(4.3-1.158x)](r2=0.9989);半效对数流速(95%CI)分别为3.595(3.561-3.628)、3.674(3.285-4.064)、3.677(3.614-3.740)和3.713(3.449-3.977).结论:随着慢性肝损伤进展,离体门脉灌流流速所决定的压力方程具有不同系数和相同形式的特征,增高半效灌流流速可建立门脉舒张潜能低下的系统生物学门脉药效干模式.

AIM： To establish equations to define portal pressure based upon perfusion velocity in isolated chronically injured rat liver. METHODS： Chronic liver injury was induced in Wistar rats using carbon tetrachloride. The liver index and pathological changes were recorded. On days 0, 28, 56 and 84 after induction of chronic liver injury, the hepatic artery, portal vein and hepatic vein were cannulated. The residual blood in the isolated liver was eliminated with Krebs-Henseleit solution through the hepatic artery. Portal vein perfusion velocities were precisely controlled between 2 500 μL/min to 15 630 μL/min with a pump. The pressure （mmHg） was monitored using the BL-420S physiological experiment system. The equations for estimating portal pressure were developed using Prism-4 software, and median velocities and their 95% confidence intervals were calculated. RESULTS： On days 0, 28, 56 and 84, the equations for estimating portal pressure （mmHg） based on the logarithmic velocity （μL/min） in isolated rat liver were y = -0.1428＋1.1423/[1 ＋10（13.805-3.84x）] （r2 = 0.9996）, y = -0.1570＋1.419/ [1＋10（4.666-1.27x）] （r2 = 0.9958）, y = 0.05106＋0.96594 /[1＋10（10.877- 2.958x）] （r2 = 0.9987）, and y = -0.09893 ＋1.406/[1＋10（4.3-1.158x）] （r2 = 0.9989）, respectively. The median velocities （95% confidence intervals） were 3.595 （3.561-3.628）, 3.674 （3.285-4.064）, 3.677 （3.614-3.740） and 3.713 （3.449-3.977）, respectively. CONCLUSION： The equations for estimating portal pressure based on the logarithmic velocity in isolated rat liver are similar at different time points during the progression of carbon tetrachloride-induced chronic liver injury. A dry model of systems biology for portal pharmacodynamics could be derived from the increased median perfusion velocities.