超声造影评估裸鼠胰腺癌微血管分布的实验研究

目的探讨超声造影评估裸鼠胰腺肿瘤内血流灌注状态的价值。方法建立人胰腺癌裸鼠原位移植瘤模型40只,应用随机数字表法分为对照组和实验组各20只,实验组动物接受重组人血管内皮抑素治疗,对照组动物接受安慰剂治疗。所有实验动物在处死前均行超声造影检查,测定两组裸鼠胰腺肿瘤组织时间-强度曲线的峰值强度(PI)和曲线下面积(AUC)。应用免疫组化法测定血管内皮生长因子(VEGF)和CD34在胰腺肿瘤组织中的相对含量;明胶-氧化铅血管造影法检测胰腺肿瘤单位体积血管密度,分析PI和AUC与血管密度指标的相关性。结果对照组裸鼠胰腺肿瘤组织的PI和AUC分别为(68.83±7.27)dB、859.93±114.27,均高于实验组(32.64±5.15)dB、523.68±57.06,差异均有统计学意义(均P<0.001)。对照组和实验组肿瘤组织中的微血管密度值分别为32.10±6.43和11.70±3.49,提示实验组中CD34阳性表达较对照组增加,差异有统计学意义(t=34.84,P<0.001);VEGF在对照组和实验组肿瘤组织中的积分光密度值分别为284.91±53.86和104.64±24.32,提示实验组中VEGF阳性含量较对照组明显降低,差异有统计学意义(t=27.13,P<0.001)。对照组和实验组胰腺肿瘤单位体积血管密度分别为6.257±1.084和1.686±0.421,差异有统计学意义(t=41.24,P<0.001)。胰腺癌组织的PI与微血管密度、单位体积血管密度均呈正相关(r=0.857、0.896,均P<0.05);AUC与微血管密度、单位体积血管密度均呈正相关(r=0.762、0.675,均P<0.05)。结论超声造影血流参数PI和AUC可准确评估裸鼠胰腺癌组织的血流灌注量,PI和AUC与胰腺癌血管密度密切相关。

Correlation between contrast-enhanced ultrasound perfusion parameters and blood perfusion status in nude mice pancreatic cancer model

Objective To explore the diagnostic value of contrast-enhanced ultrasonography in analyzing the blood perfusion status of pancreatic cancer model.Methods Forty cases of pancreatic cancer orthotopic xenograft tumor model were divided into control group(n=20)and experimental group(n=20)by random number table method.The experimental group was treated with recombinant human endostatin.The control group was treated with placebo.All animals underwent contrast-enhanced ultrasound before execution.The peak intensity(PI)and the area under the curve(AUC)were measured.Immunohistochemistry was employed to analyze the relative levels of vascular endothelial growth factor(VEGF)and CD34 in pancreatic cancer specimens.Tumor vascular imaging was conducted using the lead oxide-gelatin injection technique to detect the vascular density per unit volume of pancreatic tumor.The relations between PI and microvascular density as well as the relationships between AUC and microvascular density were analyzed.Results A significant decrease of PI and AUC were found in experimental group specimens(32.64±5.15)dB and 523.68±57.06]when compared with the control group(68.83±7.27)dB and 859.93±114.27],there were significant difference(both P<0.001).The microvascular density of control group and experimental group were 32.1±6.43 and 11.7±3.49,the positive expression of CD34 in the experimental group was significantly increased compared with control group,and the difference was statistically significant(t=34.84,P<0.001).The integrated optical density values of VEGF in control group and experimental group were 284.91±53.86 and 104.64±24.32.The positive expression of VEGF in the experimental group was significantly reduced compared with control group(t=27.13,P<0.001).The vascular density perunit volume of pancreatic tumor of control group and experimental group were 6.257±1.084 and 1.686±0.421,the difference was statistically significant(t=41.24,P<0.001).The PI were positively correlated with micro vascular density and vascular density per unit volume in pancreatic cancer tissues(r=0.857,0.896,both P<0.05).The AUC were positively correlated with micro vessel density and vascular density per unit volume in pancreatic cancer tissues(r=0.762,0.675,both P<0.05).Conclusion Contrastenhanced ultrasound parameters PI and AUC can accurately evaluate the blood perfusion of pancreatic cancer,and the values of PI and AUC are closely related to the vascular density of pancreatic cancer.