联合测定吲哚菁绿和D-山梨醇评价肝储备功能

Evaluating liver functional reserve by combining D-sorbitol with indocyanine green measurement

目的 利用高效液相法(HPLC)测定正常肝脏和肝硬化肝脏的吲哚箐绿(ICG)肝固有代谢容量,并结合D-山梨醇无创测量肝功能性血流量、肝内分流率,全面评价肝储备功能。方法 制作大鼠肝硬化模型和肝脏隔离灌注模型,据HPLC法和Bergmeyer酶分光光度法分别测量ICG和D-山梨醇的药代动力学参数。结果 (1)HPLC证实ICG包括ICG原形(ICGg)和ICG降解产物(ICGdp)两种成分,保留时间分别为8.9min和24.2min,两种成分光谱相似,但体内代谢不同。(2)据ICGg计算的肝固有代谢容量(Q_(INT,I))在对照组和肝硬化组分别为(36.57±13.03)ml/min和(14.39±5.13)ml/min,肝硬化组Q_(INT,I)明显下降(t=7.08,P<0.01)。(3)肝功能性血流量(Q_(FUNC)),肝内分流率(Q_(IHS))在对照组和肝硬化组分别为:(34.06±5.12)ml/min和(17.54±7.02)ml/min,(9.9±1.4)％和(47.5±20.9)％,肝硬化组Q_(FUNC)显著下降(t=8.41,P<0.01),Q_(IHS)显著增加(t=8.35,P<0.01)。结论(1)HPLC法可避免ICGdp的干扰,优于传统的分光光度法,能用于肝固有代谢容量测定。(2)D-山梨醇肝清除率,是无创测定正常肝脏的总血流量,和肝硬化肝脏的肝功能性血流量、肝内分流率的实用可靠方法。(3)ICG与D-山梨醇联合使用,有助于全面评价肝脏功能状态。

Objective To noninvasively evaluate hepatic functional blood flow, intrahepatic shunt rate and hepatic functional reserve in both normal and cirrhotic liver using D-sorbitol and indocyanine green measured by high performance liquid chromatography (HPLC). Methods Male Sprague-Dawley (SD) rats were divided into normal control and cirrhotic group in which the rats were administrated with tetrachloride. Then the isolated perfused liver models were established. The pharmacokinetic indexes of D-sorbitol and indocyanine green (ICG) were measured by the traditional spectrophotometry (SPEC) and HPLC respectively. Results (l)HPLC showed that ICG contained genuine ICG (ICGg) and ICG degraded products (ICGdp), which had similar spectrum but metabolic kinetics different with the retention time of 8.9 minutes and 24.2 minutes respectively. (2)Hepatic intrinsic metabolic capacity (QINT,1) was (36.57 ± 13.03) ml/min in control group and (14.39 ± 5.13) ml/min in cirrhotic group (t = 7.08, P < 0.01). (3)Hepatic functional blood flow (QFUNC) in cirrhotic group declined, compared with that in control group (34.06 ml/min ± 5.12 ml/min vs 17.54 ml/min ± 7.02 ml/min, t = 8.41, P < 0.01), while intrahepatic shunt rate (QINS) increased markedly (9.9% ± 1.4% vs 47.5% ?20.9%, t = 8.35, P < 0.01). Conclusions (1) HPLC method is superior to SPEC in measuring ICG, because it can avoid the disturbance from ICGdp, so that ICG measured by HPLC is valid for QINT, I evaluation. (2)The hepatic clearance of D-sorbitol measurement is a noninvasive and reliable method for evaluating the total blood flow in normal liver, and hepatic functional blood flow and intrahepatic shunt rate in cirrhotic liver. (3)Combining D-sorbitol with indocyanine green measurement is helpful for assessment of liver functional reserve.