索拉菲尼对肝硬化大鼠部分肝切除术后肝脏再生的影响

Effect of sorafenib on liver regeneration after partial hepatoectomy in liver cirrhotic rats

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(PDG-FR-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。

AIM：To study the effect of sorafenib on the liver regeneration after partial hepatectomy（PH） in cirrhotic rats.METHODS;Thirty Wistar rats with liver cirrhosis induced successfully with diethylnitrosamine（DEN） underwent 30%PH and then were randomly divided into 2 groups（re = 15）.The rats in experimental group were fed with sorafenib at dose of 30 mg ？ kg^（-1） ？ d^（-1） from the 1st day to the 10th day after PH,while those in control group were fed with vehicle by gavage.The blood and liver tissues of the rats were collected after PH and at the end of the experiment. Liver regeneration rate（LRR） and proliferating cell nuclear antigen（PCNA） expression were assessed for determining the hepatocyte proliferation.The content of alanine transaminase（ALT）,albumin（ALB）,total bilirubin（TBIL）,direct bilirubin （DBIL）,angiogenesis related factors including vascular endothelial growth factor（VEGF）,vascular endothelial growth factor receptor 2（VEGFR-2 ）,platelet-derived growth factor receptorβ（PDGFR -β） and micro-vessel density（MVD） were measured in both groups.RESULTS;LRRs on day 10 after PH were 45.43%±3.36%and 44.21%±2.77%in experimental group and control group,respectively（P〈0.05）,and the expression of PCNA in hepatic tissues of the rats was not found by the method of immunohistochemistry in both groups.Liver function index had no significant difference between the 2 groups（P〉0.05 ）.However,other than VEGF,sorafenib resulted in inhibition of VEGFR-2 and PDGFR -βexpression and reduction of MVD in experiment group,and significant difference between the 2 groups was observed（P〈0.01 ）. CONCLUSION：Sorafenib does not influence live regeneration after PH in liver cirrhotic rats.