DCE-MRI评价中药康莱特抑制人结肠癌裸鼠皮下移植瘤血管生成的研究

目的探讨动态增强磁共振评价中药康莱特抑制人结肠癌裸鼠皮下移植瘤血管生成的应用价值。方法建立人型结肠癌HT-29裸鼠皮下移植瘤模型48只,随机分为实验组(n=24)和对照组(n=24),实验组每日给予康莱特0.5mg/(20g.d)腹腔注射,对照组每日腹腔注射等量生理盐水,分别于治疗前、治疗后7天、14天、21天进行DCE-MRI扫描,并且在治疗后的3个时间节点扫描结束后分别处死8只取肿瘤组织进行病理免疫组化检查,动态观察并分析反映肿瘤血管功能的参数值9对比剂容积转运常数Ktrans、速率常数K_(ep)、血管外细胞外容积分数Ve、血浆空间容积分数Vp,并与同期肿瘤组织MVD表达结果进行相关性分析。结果随时间延长,实验组K~(trans)及K_(ep)值逐渐下降,对照组K~(trans)及Kep值逐渐上升,均存在统计学差异(P0.05)。治疗前实验组与对照组K~(trans)及K_(ep)值比较差异无统计学意义,治疗后的3个时间节点实验组K~(trans)及K_(ep)值分别明显低于对照组,均存在统计学差异(P0.05)。实验组及对照组给药后三个时间节点的K~(trans)及K_(ep)值均与MVD呈正相关(P均0.05)。结论康莱特对人结肠癌异体移植瘤具有良好的抑制作用,DCE-MRI技术所得到的动态变化的K~(trans)及K_(ep)值可被看做是评价结肠癌早期化疗效果的定量指标。

The Value of Dynamic Contrast-enhanced MRI in Assessing Anti-angiogenic Effect of KLT in Human Colon Cancer Transplanted Subcutaneously in Nude Mice

Objective To investigate the applicated value of dynamic contrast-enhanced MRI(DCE-MRI) in evaluating anti-angiogenic effect of Chinese medicine KLT in human colon cancer transplanted subcutaneously in nude mice. Methods 48 human colon cancer models of HT-29 which made by nude mice were established, and divided into experimental group and control group randomly, peritoneal cavities of the experimental group were injected KLT with dose 0.5mg/20g per day, and the control group were injected with the same volumes of saline in the same locations, DCE-MRI were performed before therapy and 7 days, 14 days, 21 days after treatment. 8 mouses were sacrificed respectively after MRI scanning in three time points, and pathological immunohistochemical examination were done. The following parameters(Ktrans, Kep,Veand Vp) which reflecting the tumor blood vessel functions were observed dynamically. The correlations between the changes of tumor tissue MVD and parameter values at each time point were analyzed. Results Ktrans and Kep of the experimental group decline and the control group rise gradually with the extended of time, the statistical differences in the two groups were existed(P<0.05).There were no statistically difference between Ktrans and Kep of the two groups before treatments, however, Ktrans and Kep of the experimental group were obviously lower than the control group at each time point after treatments which were statistically significances(P<0.05). Ktrans and Kep of the two groups after treatments were positively correlated with corresponded MVD at each time point(P<0.05). Conclusion KLT could inhibit the development of human colon cancer xenograft significantly, the dynamic changes of Ktrans and Kep values of DCE-MRI technology can be considered as a quantitative indexes for evaluating early colon cancer chemotherapy.