肝细胞膜上OATP和MRP载体与肝功能评价的相关性MRI实验研究

In order to prevent the acute hepatic failure after the surgery of hepatic tumor, it's one of the most core issue to exactly evaluate residual liver function before operation. Calculation of residual liver volume is still to have the limitation,namely it is not always positive correlation between liver vulume and function. Novel MR Contrast Medium(Primovist) is specificity to be taken by hepatocytes and excreted into biliary system with its half dose via peripheral venous injection after 15-20 minutes, and further more, Primovist absorption and excretion by hepatocytes is correlated with function of organic anion-transporting polypeptide(OATP) and multi-drug resistance protein(MRP) Schleppers, both of them are located on the membranes of hepatocytes,respectively. It's supposed that both of OATP and MRP are closely correlation with liver function. This study will employ the Rats to focus on investigating the relationship between experimental index of liver function and expression level of OATP and MRP with intracellular concentration of Primovist for the hepatocytes. The aim is to study quantitative assessment of liver function by 3.0T MR system and Primovist, meanwhile objective evaluation is also considered for the accuracy and influencing factors etc.The final study is to offer the optimized and more accurate imaging technique for assessment of residual liver function or segmental liver function before liver surgery in the clinical practice.

为防止肝肿瘤术后急性肝衰竭发生，术前准确评估残肝功能储备是临床关键问题之一。常规采用计算残肝体积方法仍有局限性，即肝体积与肝功能并非总是呈正性相关。新型磁共振对比剂（Primovist）经周围静脉注射后15-20分钟后，其50%剂量可特异性被肝细胞吸收和排泄入胆道系统，Primovist通过肝细胞膜上有机转运多肽(OATP)载体转运吸收，排泄则与多药耐药相关蛋白(MRP)载体有关。推测这些细胞转运多肽（蛋白）功能与肝细胞功能密切相关。本项目将采用大鼠动物模型，研究观察大鼠肝细胞膜上OATP和MRP表达水平与Primovist在肝细胞内浓度及肝功能实验指标的相关性研究，旨在利用3.0T 磁共振成像技术结合Primovist 可定量评价肝细胞功能，同时客观评价其准确性及影响因素等，为临床提供术前评价残肝或肝段性肝功能评估更客观准确的影像学技术。

本研究拟采用动物模型的建立，研究普美显增强磁共振检查定量评价肝细胞功能的潜能。本研究在执行过程中，进行相对比较顺利，基本完成了预定的目标。成功建立及优化了普美显增强磁共振检查的扫描方案（包括针对动物实验及临床患者），尤其是多个扫描序列的合理安排，扫描参数的设定，与临床检测手段相比较，论证运用普美显增强磁共振检查进行无创性肝段肝功能检测的可行性。完成了两种动物模型的制作，即胆汁淤积型动物模型的制作及非酒精性脂肪肝病动物模型的制作。在前组动物实验中发现，肝胆特异期测得的T1信号值和首过增强斜率百分比相结合，可用于评估肝外胆汁淤积性肝损伤；在后组动物实验中，采用脂肪变性、活动度和纤维化积分（steatosis, activity, and fibrosis, SAF-score）进行半定量评判，得出肝胆特异期的T1信号值可有效评估非酒精性脂肪肝病。运用普美显增强磁共振检查可进行精确、有效的肝功能的检测，与临床检测手段及病理结果相比较，论证了运用普美显增强磁共振检查进行无创性肝段肝功能检测的可行性及有效性，为临床提供术前评价残肝及肝段性肝功能更为客观及精确的影像学技术。