CO_2气腹及腹腔化疗干预对HIF-1α和VEGF在裸鼠结肠癌组织中表达的影响

Effects of carbon dioxide pneumoperitoneum and intraperitoneal chemotherapy on expression of HIF-1α and VEGF in colon carcinoma of nude mice

目的探讨CO2气腹及腹腔化疗干预对裸鼠结肠癌生长与转移的影响。方法以ZT胶粘贴法建立结肠癌裸鼠原位移植模型，10d后随机分成：麻醉控制组（A组，n=10）；CO2气腹组（B组，n=18）；CO2气腹＋腹腔化疗组（C组，n=18），腹腔化疗为气腹后第2～6天接受5-FuH＋CF灌注。二次手术后6周，观察各组实验鼠原位移植瘤生长与转移情况。采用免疫组化EnVision法检测三组结肠原位移植瘤标本中缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的表达。结果ZT胶粘贴法成瘤率100％，并可致肿瘤远处转移，各组原位移植瘤体积及腹膜穿刺孔转移情况对比有统计学差异。CO2气腹组结肠癌组织中HIF-1α和VEGF的表达水平高于其它两组（P〈0．05）。结论CO2气腹对一定生长状态的结肠癌有潜在促进生长与转移的作用，气腹术后早期腹腔化疗对此有抑制作用。CO2气腹可能是一触发因素诱导HIF-1α过度表达，进而促进VEGF表达上调，促进肿瘤血管生成。

Objective To study the effect of CO2 pneumoperitoneum and intraperitoneal chemotherapy on colon carcinoma growth and metastasis in nude mice. Methods Tumor tissue was implanted to the colon wall of mice with ZT glue to set up a model of colon carcinoma. The mice with colon carcinoma were randomized into 3 groups of anesthesia control（C）, CO2 pneumoperitoneum（A） and CO2 pneumoperitoneum with intraperitoneal chemotherapy（B）. Ten days later, the mice of group B was given an intraperitoneal chemotherapy with 5-Fluorouraeil and calcium folinate from the first postoperative day to the 5th day. Six weeks after the second operation, the mice were sacrificed for observeing tumor growth and metastasis. The expressions of hypoxia-indueible faetor-1α（HIF-1α） and vascular endothelial growth factor （VEGF） in the tumor tissues were detected by EnVision immunohistochemicat method. Results The mice all formed in situ masses of coton carcinoma and some of them had metastases. The difference of the volume of in situ tumors and port-site metastases were significant. The expression levels of HIF-1α and VEGF in the tumor tissues of group A were higher than those in the other two groups（P〈0. 05）. Conclusion With certain pressure and operation time, CO2 pneumoperitoneum seems to promote colon carcinoma growth and metastasis in some phase, which may be suppressed by intraperitoneal chemotherapy. CO2 pneumoperitoneum may be an inducible factor that makes HIF-1α overexpressed, and HIF-1α may play a role in angiogenesis and tumor progression by upregulating the expression of VEGF in colon carcinoma.