VX2肺种植瘤CT灌注与血管内皮细胞生长因子表达及血管生成相关性的实验研究

Correlation between CT perfusion parameters and expression of VEGF in implanted VX2 lung tumor

目的探讨兔VX2肺种植瘤CT灌注成像参数与血管内皮细胞生长因子(VEGF)表达情况及微血管密度(MVD)计数之间的相关性,为进一步应用CT灌注成像评价肿瘤血管生成情况及判断肿瘤预后提供理论依据。方法采用穿刺种植方法于15只兔肺内种植VX2肿瘤,20 d后选择>7 mm以上肿瘤,进行多层CT灌注扫描。应用Perfusion 3软件处理获得反映肿瘤灌注功能状态的血流量(BF)、血容量(BV)、表面通透性(PS)及最大增强值(MAV)。CT灌注扫描后处死实验兔,肺标本常规甲醛固定、石蜡包埋、5μm厚切片,行苏木素-伊红(HE)染色和免疫组织化学检查(抗CD34抗体和抗VEGF抗体染色)。所有计量资料以x-±s来表示,不同组别之间的参数比较采用t检验,相关分析采用Pearson法。结果 CT灌注成像显示兔肺种植瘤及瘤周区的BF、BV和PS值较正常肺组织有明显升高,但瘤周区PS较肿瘤区为低,因此PS图上显示的病变范围与CT增强图像显示的病变范围近似,而BF和BV图上显示的病变范围比CT增强图像上显示的病变范围要大。免疫组织化学研究表明实验兔肿瘤标本中CD34染色阳性MVD计数为68±8,而VEGF阳性细胞百分数为73±10。Pearson相关分析表明:肿瘤实质区CT灌注参数MAV、BF、BV、PS与MVD、VEGF表达呈正相关。结论 CT灌注参数不仅能反映兔VX2肺种植瘤微循环情况,而且可以反映肿瘤微血管生成情况,这可能对预测肿瘤微血管生成和转移发挥重要作用。

Objective To evaluate the correlation between CT perfusion parameters and tumor angiogenesis,expression of VEGF in implanted VX2 lung tumor.Methods VX2 tissue block were implanted in 15 healthy New Zealand rabbits.Twenty days later,the tumor,of which the diameter was over 7 mm,was scanned with 16 row spiral CT.With the software of Perfusion 3,the blood flow（BF）,blood volume（BV）,permeability surface area product（PS） and the maximum attenuation value（MAV） were calculated.After CT examination,the rabbit was sacrificed and the tumor slices were immunohistochemical stained with anti-CD34 and anti-VEGF mono-colonal antibody.The CT perfusion parameters were correlated with MVD and VEGF expression by using Pearson correlation analysis,with significance assigned at the 5% level.Results Blood supply of tumor and regions around tumor was more than those of normal lung tissue.PS value increased sharply in tumor.Although PS value of regions around tumor was also higher than that of normal lung,but lower than that of tumor.Significant positive correlation was observed between CT perfusion parameters（BF,BV,PS and MAV） and the expression of VEGF and MVD in tumor.Conclusion CT perfusion parameters could reflect the microcirculation of tumor,it also reflect the angiogenesis in the tumor.