Elevated Liver Regeneration in Response to Pharmacological Reduction of Elevated Portal Venous Pressure by Terlipressin After Partial Hepatectomy
Elevated Liver Regeneration in Response to Pharmacological Reduction of Elevated Portal Venous Pressure by Terlipressin After Partial Hepatectomy
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DOI：
10.1097/tp.0000000000000045
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发表时间：
2014-05-15
期刊：
影响因子：
6.2
通讯作者：
Beldi, Guido
中科院分区：
文献类型：
--
作者：
Fahrner, Rene;Patsenker, Eleonora;Beldi, Guido
背景肝再生对于接受活体肝移植或扩大肝切除的患者至关重要，并且可能与门静脉压力升高、肝再生受损和术后发病率相关。本研究的目的是评估特利加压素降低门静脉压力是否能改善正常和脂肪肝大鼠肝部分切除术后的术后肝再生，在啮齿动物model.Methods门静脉压力进行了评估后，轻微（30%），标准（60%），或延长（80%）部分肝切除术（PH）的小鼠和无肝脏脂肪变性。肝再生评估BrdU掺入和Ki-67 immunostaining.Results门静脉压力显着升高后PH正常和脂肪肝的小鼠相比，假手术小鼠。特利加压素降低80%PH后升高的门静脉压力与肝细胞增殖增加相关。在脂肪肝中，用特利加压素治疗的动物在30%PH后肝再生增加，在60%PH后存活增加。特利加压素可减轻PH后IL-6 mRNA表达，下调p21和GADD 45 mRNA表达，提示细胞周期抑制和细胞应激减轻。通过使用特利加压素的PH改善瘦和脂肪变性小鼠肝脏中PH后的肝再生。
Background Liver regeneration is of crucial importance for patients undergoing living liver transplantations or extended liver resections and can be associated with elevated portal venous pressure, impaired hepatic regeneration, and postoperative morbidity. The aim of this study was to assess whether reduction of portal venous pressure by terlipressin improves postoperative liver regeneration in normal and steatotic livers after partial hepatectomy in a rodent model.Methods Portal venous pressure was assessed after minor (30%), standard (60%), or extended (80%) partial hepatectomy (PH) in mice with and without liver steatosis. Liver regeneration was assessed by BrdU incorporation and Ki-67 immunostaining.Results Portal venous pressure was significantly elevated post-PH in mice with normal and steatotic livers compared to sham-operated mice. Reduction of elevated portal pressure after 80% PH by terlipressin was associated with an increase of hepatocellular proliferation. In steatotic livers, animals treated with terlipressin had an increase in liver regeneration after 30% PH and increased survival after 60% PH. Mechanistically, terlipressin alleviated IL-6 mRNA expression following PH and down-regulated p21 and GADD45 mRNA suggesting a reduction of cell cycle inhibition and cellular stress.Conclusions Reduction of elevated portal pressure post-PH by the use of terlipressin improves liver regeneration after PH in lean and steatotic mouse livers.