小剂量奥沙利铂化疗对小鼠H22肝癌乏氧的影响

The influence of low dose oxaliplatin chemotherapy on hypoxia in mouse H22 liver cancer

目的观察小剂量奥沙利铂化疗对小鼠H22肝癌乏氧动态变化的影响,并探讨乏氧改变与其抗血管生成效应的关系。方法建立小鼠H22肝癌皮下移植瘤模型,将成瘤小鼠随机分成对照组(5%葡萄糖20ml/kg)和治疗组(奥沙利铂1.5mg/kg),分别隔日腹腔给药(设为d0、d2、d4、d6)。于d1、d3、d5、d7行99mTc-HL91乏氧显像,在平面图像上通过核医学感兴趣区(ROI)技术,计算肿瘤与对侧相应部位放射性比值(T/NT)。两组于d1、d3、d5、d7分别处死小鼠,取瘤体,免疫组织化学染色检测肿瘤组织中CD34表达,连续观察d1、d3、d5、d7治疗组与对照组血管形态差异,并比较肿瘤微血管密度(MVD)的动态变化。结果对照组d1、d3、d5、d7T/NT比值分别为3.416±0.264、3.883±0.346、4.105±0.371和4.439±0.428,治疗组d1、d3、d5、d7T/NT比值分别为3.369±0.100、2.195±0.106、3.367±0.214和4.262±0.214,治疗组d3T/NT最低。对照组d1、d3、d5、d7MVD分别为30.17±1.17、33.50±1.05、37.50±1.05和40.83±1.47,治疗组d1、d3、d5、d7MVD分别为28.83±1.47、23.07±1.47、20.17±1.94和18.33±1.21。结论小剂量奥沙利铂化疗能够一过性改善乏氧,并与其抗血管生成作用一致,有可能增强肝癌放疗的疗效。

Objective To observe the influence of low dose oxaliplatin chemotherapy on dynamic oxygenation change within tumors and explore the relation between hypoxia and antiangiogenic effect.Methods Mouse tumor model was established by implanting H22 mouse hepatocarcinoma cells under skin.Experimental mice were randomly divided into two groups,including control group（5% glucose intraperitoneal injection,20ml/kg） and treatment group（1.5mg/kg oxaliplatin）.Drug was given on d0,d2,d4 and d6.Tumors were imaged using 99mTc-HL91 technique on d1,d3,d5,d7 and the radioactivity ratio of tumor to normal tissue（T/NT） were calculated using the region-interesting（ROI）technique.Mice from 2 group were killed and taken tumor tissues on d1,d3,d5,d7.The expression of CD34 was detected using immunohistochemistry staining method,by which to observe continuous disparities of vessel morphous and compare dynamic changes of microvessel density.Results The ratio of T/NT in control group were 3.416±0.264,3.883±0.346,4.105±0.371 and 4.439±0.428 on d1,d3,d5,d7,and in treatment group were 3.369±0.100,2.195±0.106,3.367±0.214 and 4.262±0.214,respectively.The MVD were 30.17±1.17,33.50±1.05,37.50±1.05 and 40.83±1.47 in control group and were 28.83±1.47,23.07±1.47,20.17±1.94 and 18.33±1.21 in treatment group.Conclusion Low dose oxaliplatin chemotherapy could improve hypoxia transiently,which accord with its antiangiogenic action.We assume its possibly normalization effect of tumor vasculature,thus further improve hypoxia,which was vital to enhance effect of radiotherapy and chemotherapy.