Division of General Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.
Liver Int. 2012 Jan;32(1):119-27. doi: 10.1111/j.1478-3231.2011.02625.x. Epub 2011 Aug 25.
Post-operative hyperbilirubinaemia in patients undergoing liver resections is associated with high morbidity and mortality. Apart from different known factors responsible for the development of post-operative jaundice, little is known about the role of hepatobiliary transport systems in the pathogenesis of post-operative jaundice in humans after liver resection.
Two liver tissue samples were taken from 14 patients undergoing liver resection before and after Pringle manoeuvre. Patients were retrospectively divided into two groups according to post-operative bilirubin serum levels. The two groups were analysed comparing the results of hepatobiliary transporter [Na-taurocholate cotransporter (NTCP); multidrug resistance gene/phospholipid export pump(MDR3); bile salt export pump (BSEP); canalicular bile salt export pump (MRP2)], heat shock protein 70 (HSP70) expression as well as the results of routinely taken post-operative liver chemistry tests.
Patients with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. HSP70 levels were significantly higher after ischaemia-reperfusion (IR) injury in both groups resulting in 4.5-fold median increase. Baseline median mRNA expression of all four transporters prior to Pringle manoeuvre tended to be lower in the low bilirubin group whereas expression of HSP70 was higher in the low bilirubin group compared to the high bilirubin group.
Higher mRNA levels of HSP70 in the low bilirubin group could indicate a possible protective effect of high HSP70 levels against IR injury. Although the exact role of hepatobiliary transport systems in the development of post-operative hyper bilirubinemia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery.
行肝切除术患者术后高胆红素血症与高发病率和高死亡率相关。除了已知的导致术后黄疸的不同因素外，对于肝切除术后患者发生术后黄疸的肝胆转运系统在发病机制中的作用知之甚少。
14 例行肝切除术患者，在阻断肝血流前后分别取 2 块肝组织标本。根据术后胆红素血清水平，将患者回顾性地分为两组。比较两组肝胆转运体[钠-牛磺胆酸共转运体（NTCP）；多药耐药相关蛋白基因/磷脂输出泵（MDR3）；胆盐输出泵（BSEP）；胆管胆盐输出泵（MRP2）]、热休克蛋白 70（HSP70）表达以及常规术后肝功能检测结果。
与术后胆红素高的患者相比，行阻断肝血流操作后，术后胆红素低的患者 NTCP、MDR3 和 BSEPmRNA 水平较低。两组缺血再灌注（IR）损伤后 HSP70 水平均显著升高，中位数增加 4.5 倍。在阻断肝血流前，所有 4 种转运体的基线中位 mRNA 表达在低胆红素组中趋于较低，而 HSP70 的表达在低胆红素组中高于高胆红素组。
低胆红素组 HSP70mRNA 水平较高，可能表明 HSP70 水平高对 IR 损伤有一定的保护作用。尽管肝胆转运系统在术后高胆红素血症发展中的确切作用尚不完全清楚，但本研究为肝手术后发生术后黄疸的分子机制提供了新的见解。
