Expression of MRP2 and MRP3 during liver regeneration after 90% partial hepatectomy in rats1
Expression of MRP2 and MRP3 during liver regeneration after 90% partial hepatectomy in rats1
复制标题
%20of%20MRP2%20和%20MRP3%20期间%20肝脏%20再生%20之后%2090%%20部分%20肝切除%20in%20大鼠1中的表达
作者：
T. Chang;K. Hakamada;Y. Toyoki;S. Tsuchida;M. Sasaki
背景成人间活体肝移植后，小体积移植物常引起受体持续性高结合胆红素血症，但其原因尚不清楚。在生理状态下，胆红素通过多药耐药蛋白（MRP）2从肝细胞分泌到胆小管，在特定情况下，通过MRP 3分泌到窦腔。本研究的目的是研究在肝再生过程中胆红素排泄模式是否有任何变化，并参考MRP 2和MRP 3的表达。方法. Sprague-Dawley大鼠进行假手术（n=37）、70%肝切除术（n=38）或90%肝切除术（n=37）。连续评估肝再生程度、总胆红素和直接胆红素、蛋白质合成和白细胞介素（IL）-6。通过Western印迹法半定量MRP 2和MRP 3的表达。结果增殖细胞核抗原标记指数显示70%和90%肝切除后肝再生迅速。血清总胆红素和直接胆红素水平显著升高（P <0.05），仅90%肝切除组出现结合型高胆红素血症。两组肝切除术后凝血因子VII下降，但早在术后12 ~ 24小时即升高。90%肝切除组血浆IL-6水平明显升高（P <0.05）。术后36和72 h，90%肝切除组MRP 2表达下降，MRP 3表达增加，而70%肝切除组MRP表达无变化。结论.在90%肝切除术后的肝再生过程中，MRP 2和MRP 3的表达降低可能在术后高胆红素血症中起重要作用。
Background. Small-for-size grafts often cause persistent conjugated hyperbilirubinemia in the recipient after adult-to-adult living donor liver transplantation, but the cause has not yet been clarified. In physiologic status, bilirubin is excreted from hepatocytes to the bile canaliculus by means of multidrug resistance protein (MRP) 2 and, in particular circumstances, by means of MRP3 to the sinusoidal space. The aim of this study was to research whether there is any change in bilirubin excretion pattern during liver regeneration with reference to expression of MRP2 and MRP3. Methods. Sprague-Dawley rats underwent sham operation (n=37), 70% hepatectomy (n=38), or 90% hepatectomy (n=37). The degree of liver regeneration, total and direct bilirubin, protein synthesis, and interleukin (IL)-6 were serially assessed. Expression of MRP2 and MRP3 were semiquantified by Western blotting. Results. The proliferating cell nuclear antigen labeling index indicated rapid liver regeneration after 70% and 90% hepatectomy. Serum levels of total and direct bilirubin increased significantly (P <0.05), and conjugated hyperbilirubinemia was proved only in the 90% hepatectomy group. Coagulation factor VII dipped but increased as early as 12 to 24 hr postoperatively in both hepatectomy groups. Plasma IL-6 levels were significantly increased in the 90% hepatectomy group (P <0.05). Expression of MRP2 was decreased and MRP3 was expressed at 36 and 72 hr postoperatively in the 90% hepatectomy group, whereas no change was observed in MRP expression in the 70% hepatectomy group. Conclusions. During liver regeneration after critical hepatectomy such as 90% hepatectomy, decrease of MRP2 and expression of MRP3 may play an important role in postoperative hyperbilirubinemia.
影响因子：
3.1
作者：
Kim, PK;Chen, J;Deutschman, CS
通讯作者：
Deutschman, CS