超声造影定量评估兔肝VX2肿瘤新生血管与CD34、血管内皮生长因子的相关性研究

Correlation evaluation of angiogenesis with CD34 and vascular endothelial growth factor in rabbit liver VX2 tumor evaluated by contrast-enhanced ultrasound

目的 分析兔肝VX2肿瘤超声造影(CEUS)定量参数与CD34和血管内皮生长因子(VEGF)的相关性,深入探讨肿瘤血管生成基础与超声造影定量参数的关系。方法 应用超声引导下经皮穿刺种植法成功复制24只兔肝VX2肿瘤模型,并通过CEUS动态观察肝肿瘤的进展过程,测定肝肿瘤超声定量参数,制作肝肿瘤标本并进行免疫组织化学染色,判定CD34和VEGF的阳性表达水平,Pearson法分析超声造影定量参数与CD34、VEGF的相关性。结果 兔肝VX2肿瘤CEUS对比剂强度、肿瘤组织与周围正常肝组织曲线增强上升斜率(AS)、达峰时间(TTP)、曲线下面积(AUC)与周围正常肝组织比较,差异有统计学意义(P <0.05),对比剂强度、AS及AUC均明显大于周围正常肝组织,VX2肿瘤TTP明显短于周围正常肝组织;TTP与CD34、VEGF呈负相关(P <0.05);对比剂强度与CD34、VEGF呈正相关(P <0.05);AS与CD34、VEGF呈正相关(P <0.05);AUC与CD34、VEGF呈正相关(P <0.05)。结论 CEUS测定的各种灌注参数,能够客观地反映肝肿瘤新生血管的生成情况及瘤内灌注特征,为影像学评估肝肿瘤血管生成、预后及复发的相关研究提供参考。

Objective To analyze the correlation between quantitative parameters of contrast-enhanced ultrasound(CEUS) and expression levels of CD34 and vascular endothelial growth factor(VEGF) in rabbit liver VX2 tumors, and to explore the relationship between the basis of tumor angiogenesis and quantitative parameters of CEUS. Methods Twenty-four rabbits with VX2 liver tumors were successfully established by ultrasound-guided percutaneous puncture and implantation. The progression of liver tumors was dynamically observed by CEUS technique. The quantitative parameters of liver tumors were measured. Tumor specimens were prepared and analyzed by immunohistochemistry. The positive expression levels of CD34 and VEGF were determined. The quantitative indexes of contrast-enhanced ultrasound, microvessel density and vascular endotheliogenesis were determined. Long factor correlation analysis. Results Comparison of contrast agent intensity(P<0.05), ascending branch slope(AS) between tumor tissue and surrounding normal liver tissye(P<0.05), peak time(TTP)(P<0.05),area under curve(AUC)(P<0.05) showed statistically significant differences(P<0.05). The intensity of contrast agent strength, AS, and AUC were significantly higher than those of surrounding normal liver tissue. Peak reaching time TTP was negatively correlated with CD34(P<0.05) and VEGF(P<0.05). Contrast agent strength was positively correlated with CD34 and VEGF(P<0.05). The AS was positively correlated with CD34 and VEGF(P<0.05). AUC under the curve was positively correlated with CD34 and VEGF(P<0.05). Conclusion Quantitative analysis of perfusion parameters by contrast-enhanced ultrasound can objectively reflect the angiogenesis and intratumoral perfusion characteristics of hepatic tumors, and provide a reference for imaging evaluation of angiogenesis, prognosis and recurrence of hepatic tumors.