特利加压素对大鼠70％肝切除后残肝再生的影响及其机制

The effect and mechanism of terlipressin on liver regeneration after 70 % hepatectomy in rats

目的 观察特利加压素对大鼠70％肝切除后残肝再生的影响及保护作用.方法 将健康雄性Wistar大鼠60只随机分为3组：A组（对照组1,n=20）,行70％肝切除;B组（对照组2,n=20）行70％肝切除＋脾切除;C组（实验组,n=20）行70％肝切除,并于术前10 min及术后3d给予特利加压素,比较各组术前、术后1、3、5、7d门静脉压力,比较各组术后血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、肝组织增殖细胞核抗原（PCNA）及促肝细胞生长素肝细胞生长因子（HGF）水平;苏木素-伊红（HE）染色观察肝脏形态学改变.结果 各组大鼠均顺利完成手术,B组术后均发生脾静脉血栓,C组及A组未见脾静脉血栓,差异有统计学意义（P＜0.01）.各组门静脉压力术后1d明显升高,其后呈逐渐下降趋势.C组术后1、3d门静脉压力低于A组及B组[（13.81 ±0.24）、（12.38±0.37）cmH2O （1cmH2O＝0.098 kPa）,P＜0.05],术后1、3d,B、C两组血清ALT、AST、TBIL水平明显低于A组（P＜0.01）,且B组低于C组（P＜0.05）;术后1d及3d,B、C两组PCNA指数明显高于A组（P＜0.01）,且B组高于C组（P＜0.05）;术后1、3d,C组血清TNF-α、IL-6水平高于于A组（P＜0.05）;术后1d及3d,B、C两组HGF水平明显高于A组（P＜0.05）,B组HGF水平高于C组（P＜0.05）.结论 特利加压素可降低肝切除术后门静脉压力,促进细胞因子TNF-α、IL-6及HGF表达,促进残肝再生并改善肝功能,避免脾切除形成门静脉系统血栓的风险.

Objective To explore the protective effect of terlipressin on liver function recovery and hepatic regeneration after 70％ hepatectomy in rats.Methods Sixty male Wistar rats weighing 230-250 g were randomly divided into three groups：group A undergoing 70％ liver resection alone; group B undergoing 70％ hepatectomy and splenectomy ; group C undergoing 70％ hepatectomy and the same dose of terlipressin.Portal veneous pressure in rats was monitored preoperatively and postoperatively at each observation time point.Blood from the inferior vena cava was used to do blood routine test and liver function test,and detect the expression of tumor necrosis factor （TNF）-cα and interleukin （IL）-6 by enzyme-linked enzyme linked immunosorbent assay （ELISA）.Part of the liver was stored in the-80 ℃ to detect the expression of hepatocyte growth factor （HGF） in the liver tissue by Western blotting; and the remaining part of liver was fixed by 4％ formaldehyde to make routine HE staining and immunohistochemical staining [liver cells：proliferating cell nuclear antigen （PCNA）].Results （1） Portal pressure in group A was significantly higher than preoperation （P ＜ 0.05）.Portal pressure in groups B and C was lower than in group A,and that in group B was lower than in group C [（13.81 ±0.24） 、（12.38 ±0.37） cmH2O,P ＜0.05] ; （2） As compared with group A,serum alanine transaminase （ALT）,aspartate aminotransferase （AST）,and total bilirubin （TBIL） levels in groups B and C were lower than in group A on the first and third day （P ＜0.05）,and those in group B were lower than in group C （P ＜ 0.05） ; （3） As compared with group A,the PCNA indexs in groups B and C group were increased on the first and third day after surgery （P ＜0.05）,and those in group B were higher than in group C （P ＜0.05） ; （4） The TNF-α and IL-6 levels in group C were lower than those in group C at first and third day postoperation （P ＜ 0.05） ; （5） HGF levels in groups B and C were higher than those in group A at first and third day postoperation （P ＜ 0.05）.Conclusion Terlipressin can lower early portal vein pressure effectively after 70％ hepatectomy,ameliorate the status of portal hyperfusion,improve liver function and promote liver regeneration.