基于肝外科术中肝脏低灌注和代谢监测的入肝血流控制研究

Liver resection is the most effective way in the treatment of various liver diseases especially primary and secondary tumors in liver surgery. Changes in liver microcirculation and metabolism, which in turn has an impact on liver function and outcome following hepatectomy, are considered essential in assessing ischemia-reperfusion injury and predicting prognosis. Based on our previous work on the noninvasive monitoring for quantification of liver perfusion, the present project will firstly establish different liver blood inflow control methods by preserving the hepatic artery or limiting portal vein, and then perform intraoperative monitor to assess the degree of liver tissue lower perfusion, oxygen saturation of hemaoglobin, and a variety of oxygen dependent metabolic parameters with Doppler ultrasound, laser Doppler blood flow, near-infrared spectroscopy and microdialysis monitoring techniques. The characteristics and regulating patterns of liver microcirculation and metabolism induced by different clamping of liver portal blood inflow will be analyzed and related to liver injury, liver function and animal survival rates. A correlation will be established between low perfusion of the liver tissue and the surgical outcome by quantitative analysis, and a value of security warning for hepatic portal clamping in rat will be suggested. This will be the first time to intraoperative assess the liver macrocirculation, microcirculation and metabolism to guide a more reasonable liver portal clamping, and will offer a new theoretical basis and surgical strategy for precise liver surgery.

肝切除术是肝脏外科治疗各种肝脏疾病特别是肝脏原发和继发肿瘤的最有效方式，而肝脏微循环和代谢的改变对于评估缺血再灌注损伤和预测预后具有重要作用，本项目在前期将非侵袭性现代监测技术引入肝胆外科领域的研究基础上，创新性地建立保留肝动脉和门靜脉限流等不同的大鼠入肝血流控制模式，拟运用超声多普勒、激光多普勒血流监测技术、近红外光谱法组织氧饱和度和微透析监测技术，术中实时监测入肝血流、肝组织低灌注程度、氧饱和度和多种低氧诱导代谢参数，分析不同入肝血流控制所致肝脏微循环和代谢的变化规律，并与再灌注后的组织病理学、肝细胞功能和动物生存率等指标进行相关性分析，建立肝组织低灌注参数与手术预后之间的定量分析模型，提出大鼠不同肝门阻断方式下的安全预警值。本课题在国内外率先通过术中实时定量评估不同肝门阻断方式所致肝组织低灌注和损伤的程度，并与术中入肝血流控制相结合，旨在为精准肝脏外科提供全新的理论基础和手术策略。

肝切除术是肝脏外科治疗各种肝胆系统疾病特别是肝脏原发和继发肿瘤的最有效方式。最彻底的根治效果与最轻的肝损伤是精准肝脏外科不懈追求的目标。通过优化肝切除时入肝血流控制方式从而减轻肝脏缺血再灌注损伤，同时监测肝脏微循环血流和组织氧饱和度的改变以评估肝脏缺血程度和预测预后有助于精准肝脏外科的实现。本项目首先在国际上最早提出了单独阻断门静脉保留肝动脉和单独阻断肝动脉门静脉限流两种新的入肝血流控制方式，并在正常大鼠、四氯化碳诱导的肝硬化大鼠和梗阻性黄疸大鼠模型上与传统肝门阻断方式进行了比较，发现新的入肝血流控制方式可以显著延长肝脏缺血耐受时间、防止肝脏发生微循环障碍和不可逆损伤，对硬化肝脏功能影响更小，具有较好的临床应用前景。项目同时还创新性地将非侵袭性的微循环监测技术引入肝胆外科领域。利用超声多普勒血流仪监测肝动脉和门静脉血流，利用激光散斑对比成像仪（LSCI）获得不同血流灌注条件下的肝脏微循环灌注的全视野成像并进行定量分析，利用近红外光谱组织氧饱和度测定仪O2C(oxygen to see)实时监测肝脏在不同灌注条件下的微循环血流和组织氧饱和度变化情况。研究结果表明LSCI测量值能够监测不同的入肝血流阻断后肝脏微循环血流的显著下降，和大鼠肝脏经历缺血再灌注损伤后微循环血流的进一步降低，与缺血再灌注肝脏的组织病理学表现一致，证明LSCI技术可以比较准确的实时反映肝脏缺血再灌注前后的微循环灌注情况，进而间接反映缺血再灌注造成的肝损伤情况。另外，利用LSCI和O2C对肝切除诱导的高灌注微循环血流进行定量监测，发现不同体积肝切除后肝组织静脉氧饱和度明显降低，组织氧饱和度与肝缺血程度密切相关，可以动态实时反映肝组织的血供情况，与扩大肝切除后的肝损伤和延迟的肝再生甚至肝衰竭相一致。这些研究结果可为精准肝脏外科的实施提供理论依据和技术支持。