应用三维彩色血管能量成像血管参数评价抗肿瘤血管生成疗效的研究

Research on three - dimensional color power angiography vascular index evaluation of anti - angiogenic effect

目的探讨乳腺癌三维彩色血管能量成像（3D—CPA）血管参数[血管指数（VI）、血流指数（FI）、血管血流指数（VFI）值]与微血管密度（MVD）、血管内皮生长因子（VEGF）之间的关系。方法40只无特定病原体（SPF）级裸鼠建立人乳腺癌移植瘤模型，1周后随机将造模成功的荷瘤鼠分为3组：生理盐水组；华蟾素、人参皂甙、三七总皂甙、香菇多糖（QHF）复方组；盐酸多柔比星组。连续给药2周后，使用3D．CPA进行扫查并获取相应的VI、FI、VFI值；处死荷瘤鼠，应用免疫组织化学检测肿瘤组织内MVD、VEGF表达；分析VI、FI、VFI值与MVD、VEGF相关性。结果（1）生理盐水组、QHF复方组、盐酸多柔比星组VI、FI、VFI平均值分别为：VI：（11．11±1．31）％、（3．91±0．59）％、（2．13±0．69）％；FI：13．00±0．91、12．00±1．31、8．80±1．19；VFI：1．47±0．16、0．47±0．12、0．18±0．07，各用药组荷瘤鼠VI、FI、VFI值较生理盐水组均明显降低，差异有统计学意义（P〈0．01）；（2）生理盐水组、QHF复方组、盐酸多柔比星组MVD、VEGF平均值分别为：MVD：47．63±4．24、29．11±4．13、26．70±4．85，VEGF：5．13±0．83、2．89±0．78、2．30±0．67，各用药组荷瘤鼠MVD计数及VEGF阳性表达较生理盐水组均明显降低，差异有统计学意义（P〈0．01）；（3）VI、FI、VFI值与MVD、VEGF表达均呈良好的线性正相关，相关系数〉0．7（P〈0．01）。结论3D—CPA血管参数可以实时、无创、客观地反应肿瘤内微循环的变化，可作为临床评价抗肿瘤血管生成药物疗效的有效方法。

Objective To study relations between vascular index [ vascularization index （VI）, flow index （ FI ）, vascularization - flow index （VFI） ] of three - dimensional color power angiography （3D-CPA） and the expression of microvessel density （MVD） and vascular endothelial growth factor （VEGF） , then to explore the feasibility of using vascular index of 3D -CPA to quantitatively evaluate anti -angiogenic effect on breast cancer. Methods Carcinoma models were built by the human breast cancer MCF -7 cells in 40 nude mice, they were randomly divided into 3 groups after modeling： saline group, QHF compound group, doxorubicin hydrochloride group. Two weeks After treatment, vascular index （VI, FI, VFI） were measured with 3D -CPA; 40 mice were sacrificed and the expressions of MVD and VEGF in the tumor tissue was detected by immunohistochemical. Then analysed the correlation between VI, FI, VFI and MVD, VEGF. Results the mean VI, FI, VFI of three groups （ saline group, QHF compound group, doxorubicin hydrochloride group） respectively ： VI ： （ 11.11±1.31 ） %, （ 3.91 ± 0. 59 ） %, （2. 13 ±0.69）% ; FI： 13.00 ±0.91, 12.00 ± 1.31, 8. 80 ± 1.19; VFI： 1.47 ±0. 16, 0.47 ±0. 12, 0. 18 ±0. 07, compared with the saline group, the VI, FI, VFI in treatment group were significantly lower, with a statistically significant difference （ P 〈 0. 01 ）. （ 2 ） the mean expressions of MVD and VEGF of three groups （saline group, QHF compound group, doxorubicin hydrochloride group） respectively： MVD： 47. 63±4. 24, 29. 11 ±4. 13, 26. 70 ±4. 85; VEGF： 5. 13 ±0. 83, 2. 89 ±0. 78, 2. 30 ±0. 67, compared with the saline group, the expressions of MVD and VEGF in each treatment group was significantly decreased, and there was a significant difference （ P 〈 0. 01 ） ; （ 3 ） VI, FI, VFI showed a positive linear correlation with the expression of MVD, VEGF, R 〉 0. 7 （P 〈 0. 01 ）. Conclusion 3D - CPA vascular index can reflect changes in the tumor microcirculation in real - time, non - invasively and objectively, thus can be used as an effective method for the clinic to evaluate the efficacy of anti - angiogenic drugs.