索拉非尼对肝切除术后早期肝再生影响的研究

Study of Impact of Sorafenib on Early Liver Regeneration Following Hepatectomy

目的探讨索拉非尼对肝切除术后早期肝再生的影响,以及癌旁肝组织VEGFR-2、VEGFR-3、PDGFR-β和C-Raf-1的表达水平与肝再生的关系。方法肝切除术后接受索拉非尼治疗的肝癌患者30例,其中12例服药剂量200 mg,18例为400 mg。应用CT测量其术后肝脏体积变化,分析不同剂量索拉非尼对术后1个月、3个月时肝再生率的影响;采用免疫组化检测癌旁肝组织中VEGFR-2、VEGFR-3、PDGFR-β和C-Raf-1表达,分析其与术后1个月、3个月时肝再生率的相关性。结果 200 mg/d组患者术后1个月、3个月时肝再生率均高于400 mg/d组患者(P<0.05)。1个月、3个月时肝再生率与VEGFR-2、PDGFR-β表达呈负相关(P<0.05),与VEGFR-3、C-Raf-1表达无相关性(P>0.05)。索拉非尼剂量及VEGFR-2表达为1个月、3个月时肝再生率的主要影响因素(P<0.01),VEGFR-2表达对肝再生率的影响最大。结论索拉非尼对肝切除术后早期肝再生有抑制作用,剂量越大抑制效果越明显。索拉非尼的抑制作用可能与通过下调VEGFR-2而抑制新生血管形成有关。

Objective To investigate the impact of sorafenib on early liver regeneration following hepatectomy as well as the association of VEGFR-2,VEGFR-3,PDGFR-β and C-Raf-1 expression in surrounding liver tissues with liver regeneration.Methods Thirty hepatocellular carcinoma（HCC） patients received sorafenib treatment after hepatectomy,12 cases were given sorafenib with a dose of 200mg and 18 cases were given sorafenib with a dose of 400mg.CT was used to measure the changes of patients’liver volume after hepatectomy,and an analysis was conducted for the impact of different doses of sorafenib on the postoperative 1-and 3-month liver regeneration rates;Immunohistochemistry was used to detect the expressions of VEGFR-2,VEGFR-3,PDGFR-β and C-Raf-1 in surrounding liver tissues,and their association with postoperative 1-and 3-month liver regeneration rate was analyzed.Results The postoperative 1and 3-month liver regeneration rates of patients received sorafenib with a dose of 200 mg daily were higher than those of patients received sorafenib with a dose of 400mg daily（P〈0.05）.The postoperative 1-and 3-month liver regeneration rates were negatively correlated with VEGFR-2 and PDGFR-β expressions（P〈0.05） and had no correlation with VEGFR-3 and C-Raf-1expressions（P〈0.05）.The dose of sorafenib and VEGFR-2 expression were the main influencing factors of postoperative 1-and 3-month liver regeneration rates（P〈0.01）,the impact of VEGFR-2 expression was the most.Conclusion Sorafenib suppresses early liver regeneration following hepatectomy,the higher dose,the more suppression on early liver regeneration.The suppression might down-regulate VEGFR-2 to inhibit neovascularization.