肝动脉阻断对大鼠肝癌血供与VEGF、MMP表达的影响  

Effects of hepatic arterial blockage on blood perfusion and VEGF and MMP-1 expression of implanted cancer in rats

作　　者：郭伟剑[1] 白永瑞[2] 林万隆[1] 顾文华[1] 张文竹[3] 成宇帆[3] 陈强[1] 郑磊贞[1] 李杰[1] 

机构地区：[1]上海第二医科大学附属新华医院肿瘤中心肿瘤科,上海市200092 [2]上海第二医科大学附属新华医院放疗科,上海市200092 [3]上海第二医科大学附属新华医院病理科,上海市200092

出　　处：《中华肝胆外科杂志》2003年第2期103-106,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：上海市科技发展基金资助 ( 0 0 41190 86 )

摘　　要：目的　观察肝动脉阻断对大鼠移植性肝癌的血液灌流与血管内皮生长因子 (VEGF)、基质金属蛋白酶 1(MMP 1)表达的影响 ,初步探索肝动脉栓塞促进肝癌转移的机制。方法　采用大鼠肝内移植Walker 2 5 6肿瘤模型 ,以肝动脉结扎 (HAL)的方法阻断肝动脉血供 ,模拟肝动脉栓塞治疗。分为对照组、剖腹对照组、HAL组。Hoechst33342标记法检测瘤组织血液灌流 (标记细胞数代表血供情况 ) ,酶联免疫吸附试验 (ELISA)测定血清VEGF水平 ,原位杂交法检测瘤组织VEGF、MMP 1表达。结果　HAL后 2d瘤组织血供明显下降 (对照组每高倍视野Hoechst33342标记细胞数 383 6± 19 2 ,HAL组 32 9 1± 2 9 3 ,P <0 0 1)。血清VEGF水平明显升高 (对照组 5 4 9± 19 3pg ml,HAL组 92 5± 43 9pg ml,P <0 0 5 )。瘤组织VEGF、MMP 1mRNA表达水平较对照组、剖腹对照组明显升高 (P <0 0 5 )。瘤组织血供与血清VEGF水平、瘤组织VEGF表达负相关。结论　肝动脉阻断使癌组织血供减少 ,转移相关基因VEGF、MMP 1表达升高。血供减少、缺氧加重可能为其诱导VEGF表达的主要机制。Objective To investigate the effects of hepatic arterial blockage on blood perfusion and VEGF and MMP-1 expression of implanted cancer in rats and explore the mechanism of transarterial embolization (TAE)-induced metastasis of liver cancer. Methods Walker 256 carcinosarcoma cells were transplanted into rat's liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Two days after HAL, blood perfusion of tumor was analyzed by Hoechst 33342 labeling assay, level of serum VEGF determined by ELISA and expression of VEGF and MMP-1 mRNA detected by in situ hybridization in the control, laparotomy and HAL groups. Results The number of Hoechst 33342 labeled cells that directly reflect blood perfusion of tumor and indirectly represent hypoxia of the tumor was significantly decreased in HAL group as compared with the control (329.1±29.3 vs 383.6±19.2, P<0.01). The level of VEGF was markedly higher in HAL group than in the control (92.5±43.9 pg/ml vs 54.9±19.3 pg/ml, P<0.05). The expression of VEGF and MMP-1 mRNA in tumor tissue was remarkably higher in HAL group than in other 2 groups (P<0.05). The blood perfusion data of tumor represented by number of Hoechst 33342 labeled cells showed a good linear inverse correlation with the level of serum VEGF and expression of VEGF mRNA in tumor tissue (P<0.05). Conclusions Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major reason for up-regulated expression of VEGF.

关 键 词：肝动脉阻断 肝癌 VEGF MMP 血管内皮生长因子 血液灌流 

分 类 号：R735.7[医药卫生—肿瘤]