碘油羟基磷灰石纳米粒对兔VX2肝肿瘤生长及血管新生的作用

The Effects of Lipiodol-hydroxyapatite Nanoparticle on Growth and Angiogenesis of Rabbit VX2 Hepatic Tumor

目的观察碘油羟基磷灰石纳米粒(nHAP)经肝动脉灌注对兔VX2肝肿瘤生长、微血管密度(MVD)及血管内皮生长因子(VEGF)表达的影响。方法100只新西兰白兔肝内肿瘤种植后2周,随机分为5组,每组20只,兔上腹正中开腹,胃十二指肠动脉插管固定,经肝动脉灌注给药,实验设生理盐水组(A组)、nHAP组(B组)、单纯碘油组(C组)、阿霉素碘油组(D组)及碘油nHAP组(E组)。治疗后1周及2周,采用CT检测并计算肿瘤的生长率,治疗后2周,病理观察肿瘤坏死率,免疫组化方法测定瘤区的MVD及VEGF表达强度。记录各组实验兔治疗后的存活期。结果治疗后1、2周,碘油nHAP组肿瘤体积及生长率明显小于其它各组(均P<0.05)。治疗后2周,碘油nHAP组肿瘤坏死率大于单纯碘油组及阿霉素碘油组(均P<0.05),分别为(80.8±12.5)%、(68.2±10.4)%、(75.3±11.6)%。单纯碘油组及阿霉素碘油组栓塞后,残余肿瘤区的MVD升高,两者分别为(33.6±7.3)和(34.9±7.7),高于生理盐水组的(22.6±6.5)(均P<0.05);两组的VEGF表达强度分别为(0.184±0.018)和(0.180±0.017),高于生理盐水组的(0.140±0.008)(均P<0.05);碘油nHAP组残余瘤区的MVD减低,VEGF表达减弱,两者分别为(16.5±3.6)和(0.104±0.003)。和其它组相比,碘油nHAP组治疗后兔的生存期明显延长(均P<0.05)。结论碘油nHAP可抑制肿瘤的生长,增加肿瘤的坏死率,抑制肿瘤血管新生,降低栓塞后残瘤VEGF表达,延长瘤兔的生存时间。

Objective To investigate the effects of lipiodol-hydroxyapatite nanoparticle （Lipi-nHAP） on growth, microvessel density （MVD） and vascular endothelial growth factor （VEGF） expression of rabbit VX2 hepatic tumor. Methods One hundred New Zealand white rabbits were randomly divided into 5 groups （n= 20 each）, and VX2 carcinoma was implanted in the left lobes of the liver. Two weeks later, abdominal exposure was carried out through an upper midline abdominal incision, a catheter was inserted into the gastroduenal artery of the rabbit with VX2 hepatic tumor, and infusion was performed via the hepatic artery using physiological saline （group A）, nHAP （group B）, Lipidol （group C）, ADM plus Lipiodol （group D）, and Lipi-nHAP （group E）. The size of tumors was observed by spiral CT scan, the volume and growth rate of tumors were calculated, and necrotic rate of tumors was assessed using pathological slices way. The values of MVD and expression level of VEGF in tumors were examined using immunohistochemistry two weeks after treatment. The survival time of the rabbits after treatment was also recorded. Results The tumor volumes and growth rate in group E at the 7th and 14th day after treatment were lower than those in other groups （P〈0.05）. The necrotic rate of tumors in group E was higher than that in other groups （P〈 0.05）. The values of MVD and expression level of VEGF were higher in groups C and D than in group A. The values of MVD and expression levels of VEGF were significantly lower in group E than other groups （P〈0.05）. The survival time in group E was longer than that other groups （P〈0.05）. Conclusion Lipi-nHAP can suppress the growth of tumors, increase the nec-rotic rate, inhibit the development of neovascularization, decrease the expression level of VEGF in residual tumors, and prolong the survival time of the rabbits with VX2 hepatic tumors.