索拉菲尼对大鼠Walker-256移植性肝癌的治疗作用  

Effect of application of Sorafenib on rat with Walker-256 hepatoma

作　　者：杨振林[1] 邹伟伟[1] 

机构地区：[1]山东滨州医学院附属医院甲状腺乳腺外科,256603

出　　处：《中华普通外科学文献（电子版）》2010年第6期32-35,共4页Chinese Archives of General Surgery(Electronic Edition)

基　　金：山东省自然科学基金资助项目(Y2007C165)

摘　　要：目的探讨索拉菲尼(Sorafenib)对大鼠Walker-256移植性肝癌的治疗作用及机制。方法 Walker-256移植性肝癌大鼠随机分为4组(n=16):A组(对照组);B组(索拉菲尼低剂量组);C组(索拉菲尼中剂量组);D组(索拉菲尼高剂量组),另设E组(正常组,n=8)。所有大鼠于术后20d取静脉血,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆红素(TB)含量;分离出肝内瘤块,称量其质量、测量其体积,计算出肿瘤的质量抑制率、体积抑制率;采用免疫组织化学方法检测瘤旁组织血管内皮生长因子(VEGF)、微血管密度(MVD)水平,并对VEGF及MVD行双变量相关性分析;对索拉菲尼各组剩余8只大鼠,观察其生存时间。结果索拉菲尼各剂量组大鼠血清ALT、AST、TB普遍低于对照组(P<0.05);C、D组大鼠瘤块体积、质量均小于A组,生存时间长于A组(P<0.05);索拉菲尼各剂量组大鼠瘤旁组织肿瘤细胞坏死程度较A组明显,癌灶周边肝脏细胞受累坏死程度较A组轻;各剂量组瘤旁组织VEGF阳性率、MVD计数小于A组(P<0.01);大鼠瘤旁组织VEGF与MVD高度相关(P<0.01),相关系数rp=0.843。结论索拉菲尼通过抑制肝癌大鼠瘤旁组织VEGF合成,降低瘤旁组织微血管密度、抑制瘤旁组织微血管生成,从而抑制肿瘤生长,减轻肿瘤对正常肝细胞的损害作用及肝功损害,延长大鼠生存期限,对大鼠移植性肝癌具有积极的治疗作用。Objective To investigate the effect and mechanism of application of Sorafenib on rat with Walker-256 hepatoma. Methods Walker-256 hepatoma 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）, and normal group （group E, n=8）. Eight 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. Weight and size of liver tumor block were measured, then the quality inhibition rate and size inhibition rate were calculated. Observations of pathological changes in tumor adjacent tissues were made with hematoxylineosin sectioning（HE）, vascular endothelial growth factor（VEGF） and microvessel density（MVD） level of tumor adjacent tissues were detected by immunohistochemistry, and bivariate correlation analysis of VEGF and MVD were used to identify their relationship. Survival time of remaining 8 rats of control group and each experimental group were observed. Results The serum level of ALT, AST, TB in experimental group were generally lower than that of control group, P〈0.05. Tumor volume and quality of middle-dose group and high-dose group were smaller than control group, P〈0.05. Compared with control group, 5orafenib experimental groups had signif- candy higher ratio of cancer cell apoptosis, lower ratio of necrosis of liver cells, VEGF-positive rate and MVD counts were smaller, P〈0.01. VEGF and MVD were highly correlated, P〈0.01, rp=0.843. Survival ratio of group C and D were higher, P〈0.05. Conclusions Sorafenib could inhibit synthesis of VEGF in tumor tissue, which inhibit augiogenesis of tumor, then tumor growth, as well as invasion to normal liver cells are inhibited, and liver function damage are slighter, survival time are prolonged, which result to a positive therapeutic effect of application of Sorafenib on rat with Walker-256

关 键 词：大鼠 肝癌 索拉菲尼 

分 类 号：R96[医药卫生—药理学] R735.7[医药卫生—药学]