AIM:To sludy lhe effecl of sorafenib on lhe liver regeneration afler parlial hepaleclomy (PH) in cirrholic rals. METHODS: Thirly Wislar rals wilh liver cirrhosis induced successfully wilh dielhylnilrosamine (DEN) un-derwenl 30% PH and lhen were randomly divided inlo 2 groups ( n = 15 ). The rals in experimental group were fed wilh sorafenib al dose of 30 mg ? Kg-1·d-1 from lhe lsl day lo lhe l0th day afler PH, while ihose in conlrol group were fed wilh vehicle by gavage. The blood and liver lissues of lhe rals were collected afler PH and al lhe end of lhe experimenl. Liver regeneralion rale (LRR) and proliferating cell nuclear anligen (PCNA) expression were assessed for determining lhe hepatocyle proliferation. The conlent of alanine Iransaminase (ALT) , albumin (ALB) , tolal bilirubin (TBIL) , direct bili-rubin (DBIL) , angiogenesis relaled factors including vascular endolhelial growth faclor ( VEGF) , vascular endothelial growlh factor receplor 2 ( VEGFR - 2) , platelel - derived growth faclor receptor (3 ( PDGFR - (3 ) and micro - vessel densily ( MVD) were measured in both groups. RESULTS: LRRs on day 10 afler PH were 45.43% ±3.36% and 44.21% ±2.77% in experimental group and conlrol group, respectively (P>0. 05) , and lhe expression of PCNA in hepatic lissues of the rals was not found by lhe method of immunohislochemistry in bolh groups. Liver function index had no significant difference between lhe 2 groups (P >0. 05) . However, other lhan VEGF, sorafenib resulted in inhibilion of VEGFR -2 and PDGFR - (3 expression and reduction of MVD in experimenl group, and significant difference belween the 2 groups was observed (P<0. 01). CONCLUSION: Sorafenib does nol influence live regeneration afler PH in liver cirrholic rals.%目的:在大鼠肝硬化模型的基础上行肝脏部分切除(PH),研究索拉菲尼(sorafenib)对大鼠肝脏再生的影响.方法:使用二乙基亚硝胺(DEN)诱导Wistar大鼠肝硬化,成功建立30只肝硬化大鼠PH模型后,随机分2组,每组15只.术后第1 d开始,分别给予实验组索拉菲尼(30 mg·kg-1·d-1)、对照组生理盐水灌胃10 d后处死.留取PH后及实验结束后的血液及肝脏标本,检测2组肝脏再生率(LRR),增殖细胞核抗原(PCNA),生化指标:丙氨酸转移酶(ALT)和血清白蛋白(ALB)、血清总胆红素(TBIL)和血清直接胆红素(DBIL)的变化,血管生成相关因子:血管内皮生长因子(VEGF)、血管内皮生长因子受体2(VEGFR-2)、血小板源性生长因子受体β(PDGFR-β),以及肝脏微血管密度(MVD)的变化.结果:(1)LRR在实验组及对照组分别为45.43%±3.36%和44.21%±2.77%,无显著差异(P>0.05);(2)免疫组织化学(IHC)没有检测到PCNA;(3)2组的生化指标无显著差异(P>0.05);(4)实验组VEGFR-2和PDGFR-β的表达受到抑制,MVD降低,并且实验组与对照组差异有统计学意义(P<0.01).结论:索拉菲尼虽然对肝硬化血管再生相关因子有抑制作用,但是对肝细胞再生和肝功能没有明显影响.
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