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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 To study the pharmacokinetics of D sorbitol in vivo and evaluate the rationality of D-sorbitol in the measurement of hepatic functional blood flow and intrahepatic shunt in normal and cirrhosis liver and to explore its clinical value and method. Methods Sixty male Sprague-Dawley rats were divided into cirrhosis group (40) and normal control group (20). After continuous intravenous infusion of D-sorbitol, blood samples were collected at different times and collected by enzyme spectrophotometry The concentration of sorbitol and urinary concentration were measured by spectrophotometry, and the total sorbitol removal rate (CLTOTAL) and sorbitol clearance rate (CLREN) were calculated in normal rats and cirrhosis rats to get the hepatic clearance rate (CLH) . Then, the portal vein pressure (PVP) was measured by cesarean section. At the same time, a model of isolated hepatic perfusion was made. KH solution containing 0 3 95 mmol·L-1 sorbitol was used as perfusate. The concentration of sorbitol in perfusate and effluent was measured, Rate (E), total hepatic blood flow (QTOTAL) and intrahepatic shunt (RINS). RESULTS ① Sorbitol was given intravenously, and the steady-state plasma concentration was reached after 120 minutes, with the normal group (0 2 0 9 ± 0 0 43) mmol·L -1 and the cirrhosis group 0 3 34 ± 0 0 7 mmol·L-1. ② The normal rats PVP = (0 94 ± 0 1 9) kPa; E = (90 .1 ± 7.2)%; CLH = (3 4.06 ± 5 .1 2) mL · min-1; QTOTAL = (3 7.8 ± 5 .44) mL · min-1; RINS = (9.9 ± 1.4)%. (3) The PVP of cirrhotic rats was (156 ± 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)