Sorafenib对肝癌肝移植术后肿瘤转移复发大鼠的治疗作用  

Treatment of Sorafenib on rat with recrudescent liver cancer after liver transplantation

作　　者：邹伟伟[1] 杨振林[1] 程凯[1] 

机构地区：[1]滨州医学院附属医院甲状腺乳腺外科,山东滨州256603

出　　处：《中国现代普通外科进展》2011年第2期85-89,共5页Chinese Journal of Current Advances in General Surgery

基　　金：山东省自然科学基金项目(Y2007C165)

摘　　要：目的:探讨Sorafenib对肝癌肝移植术后肿瘤转移复发大鼠的治疗作用。方法:Walker-256癌细胞于Wistar大鼠门静脉注射,模拟大鼠肝癌肝移植术后肿瘤转移复发模型,术后随机分为4组(n=16):对照组、Sorafenib低剂量组、Sorafenib中剂量组、Sorafenib高剂量组,另选取5只正常Wistar大鼠作为正常组。Sorafenib各剂量组和对照组分别于术后20 d各随机选取8只,抽取静脉血,采用酶联免疫吸附方法(ELISA)检测大鼠血清中血管内皮生长因子(VEGF)含量,检测大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆红素(TB)含量;取大鼠肝脏,常规甲醛固定、制作石蜡切片,HE染色,常规镜下观察;采用免疫组织化学方法计数肝脏微血管密度(MVD);观察Sorafenib各剂量组及对照组剩余8只大鼠生存时间。结果:Sorafenib各剂量组及对照组大鼠肝脏均出现了肿瘤转移复发,但Sorafenib各剂量组大鼠肝脏癌灶坏死程度较对照组明显,癌灶周边肝脏细胞受累坏死程度较对照组轻;Sorafenib各剂量组大鼠血清VEGF、ALT、AST、TB浓度均低于对照组(P<0.05);Sorafenib各剂量组大鼠肝脏MVD计数低于对照组(P<0.05);Sorafenib中、高剂量组大鼠存活率高于对照组(P<0.05)。结论:Sorafenib可以抑制肝癌肝移植术后肿瘤转移复发大鼠癌灶微血管生成,同时减轻癌灶对正常肝细胞的损害作用,延长肝癌肝移植术后肿瘤转移复发大鼠的生存时间,对肝癌肝移植术后肿瘤转移复发大鼠起到一定的治疗作用。Objective： To investigate the treatment of tumor recurrence with Sorafenib after orthotopic liver transplantation for primary carcinoma of liver in rats.Methods： Portal vein injection of Walker-256 cancer cells to establish models of metastasis and recurrence of liver after liver transplantation in rat.The rats were randomLy divided into 4 groups（n=16）：Control group（group A）,Sorafenib low-dose group（group B）,Sorafenib middle-dose group（group C）,Sorafenib high-dose group（group D）,moreover,a normal group（group E,n= 5）.Eight rats of each group were chosen 20 days after operation to have observation of pathological changes in liver,which were made with hematoxylin-eosin sectioning（HE）;8 rats of each group were chosen 20 days after operation to test the alanine amino transferase（ALT）,aspartate aminotransferase（AST） and bilirubin（TB） of vein blood;The serum level of vascular endothelial growth factor（VEGF） were tested by enzyme linked immunosorbent assay（ELISA）;microvessel density（MVD） level of liver tissues were detected by immunohistochemistry;survival time of remaining 8 rats from control group and experimental groups of Sorafenib were observed.Results： There were no differences in tumor metastasis and recurrence among control group and Sorafenib experimental groups,for it could be found metastasis and recurrence in rat liver of each group,however,Sorafenib experimental groups had signifcantly higher ratio of cancer cell apoptosis,lower ratio of necrosis of liver cells compared with control group;The serum level of ALT、AST、TB in each experimental group of Sorafenib were generally lower than that of control group（P〈0.05）,Serum level of VEGF in each experimental group of Sorafenib were generally lower than that of control group（P〈0.05）,MVD counts of liver in each experimental group were smaller than that of control group（P〈0.05）,survival rate of middle-dose group and high-dose group were higher（P〈0.05）.Conclusions： Sorafenib can

关 键 词：大鼠 Wistar 肝肿瘤 肝移植 SORAFENIB 

分 类 号：R735.7[医药卫生—肿瘤]