血管生成抑制剂烟曲霉素衍生物在介入治疗肝细胞癌实验中的应用

目的研究经肝动脉化疗栓塞术结合肝动脉灌注血管生成抑制剂合成的烟曲霉素衍生物（TNP-470）治疗ACI大鼠肝细胞癌的疗效。方法在20只雄性ACI大鼠肝包膜下移植Morris Hepatoma3924A肝癌小瘤块（2mm^3），移植术后第13天时进行MR检查，测量肿瘤体积V1，第14天时，在荷瘤大鼠经胃十二指肠动脉逆行插管至肝动脉而采取以下介入治疗方案：治疗组：碘化油（0．1ml）＋丝裂霉素（0．1mg）＋TNP-470（5．0mg）（10只）；对照组：碘化油（0．1ml）＋丝裂霉素（0．1mg）（10只）。治疗后再次进行MR检查测量肿瘤体积V2，比较肝肿瘤体积变化（V2／V1）。结果治疗组和对照组大鼠经介入治疗前后的肝肿瘤平均体积分别为0．04cm^3和0．15cm^3以及0．04cm^3和0．34cm^3。治疗组和对照组肿瘤体积平均增长倍数（V2／V1）分别为4．11和9．14。与对照组相比，治疗组能明显抑制肝肿瘤体积的增长（P〈0．01）。结论在ACI大鼠肝细胞癌模型，采用肝动脉化疗栓塞术结合肝动脉灌注血管生成抑制剂TNP-470的治疗方法可明显抑制肝肿瘤体积的生长。

The application of TNP-470 as an antiangiogenesis drug in the experiment of interventional therapy of hepatocellular carcinoma

Objective To assess the value of transarterial chemoembolization (TACE) combined with transarterial administration of TNP-470 as an antiangiogenesis drug for treating hepatocellular carcinoma (HCC) in ACI rats. Methods A solid Morris Hepatoma 3924A (2 mm3) was implanted into the liver of 20 male ACI rats. MRI was performed and the volume of the tumor (V1) was measured on the 13th day in all rats. After laparotomy and retrograde placement of a microcatheter into the gastroduodenal artery, the following agents were injected into the hepatic artery via the gastroduodenal artery (14 days after implantation): (A) Mitomycin (0.1 mg) + Lipiodol (0.1 ml) + TNP-470 (5.0 mg) (n=10, experimental group); (B) Mitomycin (0.1 mg) + Lipiodol (0.1 ml) (n=10, control group). The tumor volumes before (V1) and after treatment (V2) were determined by MRI and the tumor growth ratio (V2/V1) was calculated. Results The mean tumor volume V1 and V2 were 0.04 cm3 and 0.15 cm3 in group A, 0.04 cm3 and 0.34 cm3 in group B, respectively. After interventional therapy, the resulting mean ratio of V2/V1 was 4.11 in group A and 9.14 in group B, respectively. Compared with group B (control group), group A showed very significant inhibition of tumor growth within the period of observation (P<0.01). Conclusion The growth of HCC can be obviously reduced by utilizing the combined TACE and transarterial administration of TNP-470 for treating HCC in ACI rats.