超声造影定量参数评价抗血管生成药治疗裸鼠胆囊癌的疗效

Anti-angiogenic therapy for gallbladder carcinoma using contrast enhanced ultrasound

目的探讨超声造影定量评价胆囊癌抗血管生成治疗效果的可行性。方法建立人胆囊癌裸鼠移植瘤模型，随机分为药物干预组及对照组。药物干预组腹腔注射重组人血管内皮抑制素（Endostar），10mg·kg^-1·d^-1，连续两周。超声造影检查两组裸鼠移植瘤，通过时间强度曲线测定到达时间（AT）、达峰时间（TTP）、峰值强度（PI）、曲线下面积（AUC）。免疫组化检查瘤块微血管密度（MVD）、血管内皮生长因子（VEGF）表达情况，比较药物干预组与对照组的差异，进一步分析超声参数与MVD、VEGF的相关性。结果药物干预组超声造影峰值强度为（10．8±5．5）dB，对照组为（16．8±5．8）dB，药物干预组明显低于对照组（P〈0．05）；两组AT、TTP、AUC差异无统计学意义。药物干预组瘤块MVD计数为8．5±3．8，对照组为13．1±3．5，药物干预组明显低于对照组（P〈0．05）；药物干预组瘤块VFGF表达是4．3±0．5分，明显低于对照组4．7±0．4分（P〈0．05）。药物干预组MVD、VEGF与超声造影参数PI呈正相关（分别为r=0．712，P〈0．05；r=0．739，P〈0．05）。结论抗血管生成药Endostar对胆囊癌生长有明显的抑制作用，峰值强度可作为评价抗血管生成疗效的有妁指标。

Objective To evaluate the feasibility of contrast enhanced ultrasound （CEUS） in gallbladder carcinoma anti-angiogenesis treatment. Methods Subcutaneous gallbladder carcinoma model was consturcted. The mice were divided into intervention-drug group and control group randomly. The mice of intervention-drug group were treated with Endostar （10 mg ·kg^-1·d^-1 ） by intraperitoneal injection for two weeks. Two groups of mice were detected by CEUS, then the time of arrival （AT）, peak time （TIP）, peak intensity （PI）, area under the curve （AUC） were measured via time-intensity curve. Expression of MVD and VEGF both in the intervention and control groups were studied through immunohistochemistry, and the correlations between MVD, VEGF and CEUS parameteres were further analyzed. Results The mean values of PI in drug intervention group and control group were 10.8 ± 5.5 and 16.8 ± 5.8, respectively. The values of PI in intervention-drug group were lower than that in control group significantly （ P 〈 0.05 ）. There was no significant difference in AT, TTP, AUC between the two groups. The mean values of MVD on drug intervention group and control group were 8.5 ± 3.8 and 13.1±3.5, respectively. The mean values of VEGF on drug intervention group and control group were 4.3± 0.5 and 4.7 ± 0.4, respectively. The values of MVD and VEGF in intervention-drug group were significant lower than that control group （P 〈 0.05 ）. MVD and VEGF values of intervention-drug group were correlated with PI （ r = 0. 712, P 〈 0. 05 ; r =0. 739, P 〈 0. 05）. Conclusion Endostar can inhibit the growth of gallbladder carcinoma and PI can be used as an effective marker to evaluatethe effect of anti-angiogenic therapy in gallbladder carcinoma.