三氧化二砷对CO_2气腹下小鼠肿瘤腹壁戳口种植影响的实验研究

An experimental study on effects of arsenic trioxide on port-site metastasis under carbon dioxide pneumoperitoneum in a murine model

目的研究腹腔内注射三氧化二砷(arsenic trioxide,As2O3)对小鼠CO2气腹下肝癌H22转移的影响。方法昆明鼠40只(清洁级),中腹部穿刺置入1mm套管针,自套管针注入1×106肿瘤细胞后,建立CO2气腹,压力8mm Hg,时间30min。术后随机分4组,每组10只,分别腹腔内注入:生理盐水,1ml;As2O3(2mg/kg),1ml;As2O3(4mg/kg),1ml;As2O3(4mg/kg)+肝素(10U/ml),共1ml。气腹后第3、7天测量肿瘤黏附因子(CD44)、血管内皮生长因子(vascular endothelial growthfactor,VEGF)的变化;比较各组生存状态、腹围、体重变化及转移瘤直径。结果气腹后第3、7天,与对照组相比,各As2O3组CD44、VEGF表达均明显降低(P<0.05)。2个高剂量组的气腹后第3天VEGF、第7天CD44比低剂量组降低明显(P<0.05)。4组戳口种植率分别为9/10、8/10、7/10、6/10,差异无显著性(χ2=2.667,P=0.446)。结论As2O3对CO2气腹腹腔镜肿瘤生长转移有抑制作用。

Objective To study the influence of intraperitoneal instillation of arsenic trioxide （As2O3 ） on metastasis of hepatoma cell line H22 under CO2 pneumoperitoneum in mice. Methods The experiment included 40 Kunming mice （cleaning inbred strain）. A 1 mm trocar was punctured through the middle abdomen, by which 1 × 10^6 tumor ceils were administered. Pneumoperitoneum was established with carbon dioxide at the pressure of 8 mm Hg over 30 min. Afterwards, the mice were randomly divided into four groups with 10 mice in each group, receiving intraperitoneal instillation with one of the following： normal saline （ 1 ml）, As2O3（2 mg/kg, 1 ml）, As2O3 （4 mg/kg, 1 ml）, or As2O3 （4 mg/kg） with heparin （10 U/ml） （1 ml totally）. Levels of CD44 and vascular endothelial growth factor （VEGF） were measured on the 3rd and 7th day after pneumoperitoneum, respectively. And the survival condition, abdominal circumference, body weight, and diameter of metastatic tumor were compared among the four groups. Results Compared with control group, significantly lower expressions of CD44 and VEGF were observed the other three groups on the 3rd and 7th day after pneumoperitoneum （P 〈 0. 05 ）. Compared with the low-dose As2O3 group, the two high-dose As2O3 groups presented significantly lower levels in VEGF on the 3rd day and in CD44 on the 7th day （ P 〈 0.05 ）. The port-site implantation rates were 9/10, 8/10, 7/10, and 6/10 in the four groups, respectively, without significant difference between each other （χ^2 = 2.667 ,P = 0.446）. Conclusions Arsenic trioxide has effects for inhibiting tumor growth and metastasis under CO2 pneumoperitoneum.