索拉非尼对肝癌术后早期肝再生的影响

Effect of sorafenib on early liver regeneration after hepatectomy

目的研究索拉非尼对肝癌患者术后早期肝再生、肝功能及凝血功能的影响,以及癌旁肝组织的血管内皮生长因子受体2(VEGFR-2)、血管内皮生长因子受体3(VEGFR-3)、血小板衍生的生长因子受体β(PDGFR-β)和原癌基因丝苏氨酸蛋白激酶1(C-Raf-1)的表达水平与肝再生的关系。方法 30例经病理确诊为肝细胞癌的患者,手术切除后接受不同剂量索拉非尼治疗。应用CT测量术后肝脏体积变化,比较不同剂量的索拉非尼对术后1、3个月时肝再生率的影响。分析不同剂量下,服药前及服药后1个月、3个月时患者肝功能及凝血功能的变化。通过免疫组化检测癌旁肝组织中VEGFR-2、VEGFR-3、PDGFR-β和C-Raf-1的表达,分析表达水平与术后1、3个月时肝再生率的相关性。结果索拉非尼服药剂量400 mg/d组的患者术后1个月、3个月时肝再生率平均增加量高于800 mg/d组的患者(P<0.05)。两组患者服药后3个月时血清AST、ALT明显比服药前升高,血清凝血酶原时间(PT)明显延长(P<0.05)。术后1、3个月时肝再生率与VEGFR-2、PDGFR-β表达呈负相关(P<0.05),VEGFR-2表达对肝再生率的影响最大。结论索拉非尼对肝癌术后早期肝再生有抑制作用,剂量越大抑制效果越明显。VEGFR-2是索拉非尼抑制早期肝再生的主要影响因素。

Objective To investigate the effect of sorafenib on early liver regeneration,liver function and coagulation function after hepatectomy,and the relationship between vascular endothelial growth factor receptor（VEGFR-2 and-3）,platelet-derived growth factor receptor（PDGFR-β）,C-Raf-1 and liver regeneration. Methods Thirty HCC patients confirmed by pathology received sorafenib treatment after hepatectomy. The liver size was measured by computed tomography to analyze the effect of different doses of sorafenib on liver regeneration. The changes of liver function and coagulation function were analyzed 1 month and 3 months after surgery. Detection of the expression of VEGFR-2,VEGFR-3,PDGFR-β and C-Raf-1 in surrounding liver tissue was performed to analyze their relations with liver regeneration rate. Results The liver regeneration rate 1- and 3-month after hepatectomy in patients received sorafenib 400 mg daily were higher than those who received 800 mg daily. The liver regeneration rate 1- and 3-month after hepatectomy was negatively correlated with VEGFR-2 and PDGFR-β（P0.05） and had no correlation with VEGFR-3 and C-Raf-1. The dose of sorafenib and level of VEGFR-2 were the main impact factors of liver regeneration rate 1- and 3-month after hepatectomy,especially VEGFR-2. Conclusions Sorafenib suppresses early liver regeneration after hepatectomy,the higher dose,the more suppression. VEGFR-2 is the main factor suppressing early liver regeneration.