D-山梨醇肝清除率评价肝功能性血流量的实验研究

Experimental study of hepatic functional blood flow evaluated by hepatic clearance of D-sorbitol

目的 通过动物实验研究D 山梨醇体内的药代动力学 ,评价其在测量正常和肝硬化肝脏的肝功能性血流量、肝内分流率方面的合理性 ,并探讨其临床应用价值和方法。方法 雄性SD大鼠 60只 ,分为肝硬化组 (4 0只 )和正常对照组 (2 0只 ) ,持续静脉滴注D 山梨醇后 ,在不同时间分别采血和收集尿液 ,采用酶分光光度法测量山梨醇血浓度和尿浓度 ,计算正常大鼠和肝硬化大鼠的山梨醇整体清除率 (CLTOTAL)、山梨醇肾清除率 (CLREN) ,从而得出山梨醇肝清除率(CLH)。然后剖腹测量门静脉压 (PVP) ,同时制作肝脏隔离灌注模型 ,采用含山梨醇 0 3 95mmol·L-1的KH液为灌流液 ,分别测量灌流液和流出液的山梨醇浓度 ,计算出肝摄取率 (E)、肝总血流量 (QTOTAL)和肝内分流率 (RINS)。结果 ①静脉滴注山梨醇 ,1 2 0min后达稳态血药浓度 ,正常组 (0 2 0 9± 0 0 43 )mmol·L-1,肝硬化组 (0 3 3 4± 0 0 7)mmol·L-1。②正常大鼠PVP =(0 94± 0 1 9)kPa;E =(90 .1± 7.2 ) % ;CLH =(3 4.0 6± 5 .1 2 )mL·min-1;QTOTAL =(3 7.8±5 .44)mL·min-1;RINS=(9.9± 1 .4) %。③肝硬化大鼠PVP =(1 5 6± 0 3 7)kPa;E =(63 8±9 8) % ;CLH=(2 1 3 1± 7 0 2 )mL·min-1;QTOTAL =(3 3 41± 9 71 )mL·min-1;RINS=(3 6 2±9 6)

Objective By the pharmacokinetic study of D sorbitol in animal experiment, to evaluate its rationality for measurement of hepatic blood flow and explore the clinical practical value and method. Methods Sixty male SD rats were divided into hepatic cirrhotic group and control group. After intravenous infusion of D sorbitol, the blood samples of these rats were extracted and their urine was collected respectively at different times for analysis. Total clearence(CL TOTAL ), renal clearence(CL REN ) and hepatic clearence(CL H) were calculated according to enzymatic spectrophotometric method. Then the isolated perfused hepatic models were made for measurement of hepatic extractive ratio E, at the same time, the hepatic total blood flow(Q TOTAL ) and intrahepatic shunt rate(R INS ) were calculated. Results ①The steady state of blood concentration was achieved within 120 mins after constant intravenous infusion of D sorbitol(0.209±0.043)mmol·L -1 in control group and(0.334±0.07)mmol·L -1 in cirrhotic group. ②In control group, PVP=(0.94±0.19)kPa, E=(90.1±7.2)%, CL H=(34.06±5.12)mL·min -1 , Q TOTAL =( 37.8 ± 5.44 )mL·min -1 and R INS =(9.9±1.4)%. ③In cirrhotic group, PVP=(1.56±0.37)kPa, E=(63.8±9.8)%,CL H=(21.31±7.02)mL·min -1 , Q TOTAL =(33.41±9.71)mL·min -1 and R INS =(36.2±9.6)%. ④PVP and R INS were elevated, while E and CL H were decreased significantly in cirrhotic group. There was no statistical diffetence of Q TOTAL between the two groups. Conclusion The hepatic clearence of D sorbitol can be measured by noninvasive steady infusion, and it can be reliably used for evaluation of hepatic functional blood flow and intrahepatic shunt rate of normal or cirrhotic liver.