超声造影评价“合欢皮298”对小鼠移植瘤血管生成的作用

Evaluating the effects of Albizia Julibrissin 298 on the angiogenesis by contrast-enhanced ultra-sonography in mice xenograft model of hepatocelluar carcionma

目的探讨超声造影评价抗肿瘤血管生成疗效的可行性。方法建立20只小鼠皮下H22肝癌异种移植瘤模型。24h后,治疗组使用"合欢皮298"5mg.kg-1.d-1灌胃治疗,连续7d,对照组给予等量生理盐水。在服药后第7天和14天分别对小鼠进行常规超声及超声造影检查,使用Sonoliver软件获得造影时间强度曲线(TIC),比较TIC参数的差异。于第14天超声造影检查完成后处死小鼠,完整剥离肿瘤,免疫组化检测肿瘤CD31表达情况,分析微血管密度(MVD)与超声造影参数的相关性。结果治疗组肿瘤体积小于对照组(P<0.05);第7天和14天,治疗组小鼠CEUS定量参数最大峰值强度(IMAX)小于对照组(P<0.01)。第14天,治疗组RT、TTP、mTT大于对照组,治疗组MVD明显少于对照组(P<0.01);MVD与IMAX呈正相关(r=0.73,P<0.01)。结论超声造影能客观反映肿瘤内微循环的灌注变化,用于临床抗肿瘤血管生成疗效观察方便易行。

Objective To investigate the feasibility of evaluating the efficacy of antitumor angiogenesis by contrast-enhanced ultra-sonography （CEUS）. Methods The xenograft model of hepatocelluar carcionma was established by subcutaneously implanting H22 cells in 20 mice. The model mice were treated by feeding Albizia Julibrissin 298 5 mg · kg1· d1 for 7 days （group A, 10 mice） or equivalent volume of normal saline as control （group B, 10 mice）. The size of the xenografts was measured by CEUS on the 7th and 14th day after drug administration. With the software of SonoLiver, the time-intensity curve（TIC） and the peffusion parameters of the maximum intensity（IMAX）, rise time（RT）, time to initial peak（TTP） and mean transit time （mTT） were obtained. On the 14th day, the mice were euthanized and the xenografts were taken out for detecting the expression of CD31 and analyzing the correlation between CEUS parameters and microvascular density（MVD）. Results The tumour volume of group A was less than that of group B（P〈0. 05）. The IMAX on the 7th and 14th day was less in group A than that in group B （P〈0. 05）. On the 14th day,the RT, TTP and mTT were greater, but MVD was less, in group A than those in group B （P%0. 01）. MVD was positively corrected with IMAX （r=0. 73,P〈0. 01）. Conclusion CEUS is an useful noninvasive and feasible tecnique for evaluating the efficacy of antitumor angiogenesis.