肝动脉阻断对大鼠移植性肝癌血液灌注及VEGF、MMP-1表达的影响

Influence of hepatic arterial blockage on blood perfusion and VEGF, MMP-1 expression of implanted liver cancer in rats.

作者信息

Guo Wei-Jian, Li Jie, Ling Wan-Long, Bai Yong-Rui, Zhang Wen-Zhu, Cheng Yu-Fan, Gu Wen-Hua, Zhuang Jun-Yan

机构信息

Department of Oncology, Xinhua Hospital of Shanghai Second Medical University, 1665 Kongjiang Road, Shanghai 200092, China.

出版信息

World J Gastroenterol. 2002 Jun;8(3):476-9. doi: 10.3748/wjg.v8.i3.476.

DOI:10.3748/wjg.v8.i3.476

PMID:12046073

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4656424/

Abstract

AIM

To investigate the influence of hepatic arterial blockage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the mechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily.

METHODS

Walker 256 carcinosarcoma was transplanted into rat liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood perfusion of tumor in control, laparotomy control, and HAL group was analyzed by Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization.

RESULTS

Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group decreased significantly compared with that in control group (329+/-29 vs 384+/-19, P<0.01). The serum VEGF level in the HAL group increased significantly as against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19 ng.L(-1), P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P<0.05). The blood perfusion data of the tumor, represented by the number of Hoechst 33342 labeled cells, showed a good linear inverse correlation with the serum VEGF level (r=-0.606, P<0.05) and the expression of VEGF mRNA in the tumor tissue ( r =-0.338, P<0.01).

CONCLUSION

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 cause of up-regulated expression of VEGF.

摘要

目的

探讨肝动脉阻断对大鼠肝移植癌血流灌注及血管内皮生长因子（VEGF）和基质金属蛋白酶-1（MMP-1）表达的影响，初步探讨经动脉栓塞（TAE）诱导肝癌转移的机制。

方法

将Walker 256癌肉瘤移植到大鼠肝脏建立肝癌模型。采用肝动脉结扎（HAL）阻断肝动脉血供并模拟TAE。通过Hoechst 33342标记法分析对照组、开腹对照组和HAL组肿瘤的血流灌注，采用ELISA法检测血清VEGF水平，原位杂交法检测VEGF和MMP-1 mRNA的表达。

结果

HAL术后2天，HAL组中代表肿瘤血流灌注及间接反映肿瘤缺氧情况的Hoechst 33342标记细胞数量较对照组显著减少（329±29 vs 384±19，P<0.01）。HAL组血清VEGF水平较对照组显著升高（93 ng·L-1±44 ng·L-1 vs 55 ng·L-1±19 ng·L-1，P<0.05）。HAL组肿瘤组织中VEGF和MMP-1 mRNA的表达较对照组和开腹对照组显著增加（P<0.05）。以Hoechst 33342标记细胞数量表示的肿瘤血流灌注数据与血清VEGF水平呈良好的线性负相关（r=-0.606，P<0.05），与肿瘤组织中VEGF mRNA的表达也呈负相关（r=-0.338，P<0.01）。