三氧化二砷-碘油化疗栓塞对兔肝移植瘤转移及与血管形成关系的研究

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目的观察三氧化二砷(As_2O_3)-碘油经肝动脉化疗栓塞对兔 VX_2肝移植瘤生长及转移的影响及与血管形成的关系。方法 48只家兔肝内肿瘤种植后2周,完全随机法分为4组,经肝动脉插管分别给予不同处理,实验设生理盐水灌注组、单纯碘油栓塞组、阿霉素-碘油栓塞组及 As_2O_3-碘油栓塞组。治疗后1周,免疫组织化学测定肿瘤区的微血管密度(MVD),治疗后3周,测量计算肝移植瘤的体积、坏死面积,观察肝内、双肺及其他器官肿瘤转移的发生率。结果治疗后1周,各组MVD 分别为(21.8±5.3)、(23.4±3.9)、(22.4±4.50)、(14.3±3.4)条/400倍视野(F=11.246,P=O.000),As_2O_3-碘油栓塞治疗组与其他组相比差异有统计学意义;肿瘤植入后5周,各处理组肿瘤体积分别为(35.5±7.1)、(21.2±8.3)、(20.7±9.1)、(11.8±3.7)cm~3(F=21.203,P=0.000),单纯碘油栓塞组、阿霉素-碘油栓塞组及 As_2O_3-碘油栓塞组与生理盐水灌注组相比差异有统计学意义(q 值分别为6.723、6.940、11.119,P<0.05),As_2O_3-碘油栓塞组与单纯碘油栓塞及阿霉素-碘油栓塞组相比差异有统计学意义(q 值分别为4.398、4.178,P值均<0.05);各组肿瘤坏死面积间差异无统计学意义(F=1.284,Jp=0.292);As_2O_3-碘油栓塞治疗组双肺转移结节数目少于其他组(H=14.983,P=0.002),结节直径小于其他组(F=4.580,P=0.007),差异有统计学意义。腹腔转移淋巴结记分显示 As_2O_3-碘油栓塞治疗组腹腔淋巴结转移少于其他组(H=9.148,P=0.027)。双肺转移结节的数目、直径及腹腔转移淋巴结与肿瘤的微血管密度呈正相关(P<0.05)。结论 As_2O_3-碘油联合经肝动脉栓塞治疗,抑制兔肝移植瘤的生长,抑制肿瘤的肺及腹腔淋巴结转移,其抑制转移的机制可能与抑制肿瘤血管形成有关。 Objective To observe the effect of arsenic trioxide (As_2O_3) -iodol oil on the growth and metastasis of VX 2 transplanted tumor in rabbits by transcatheter arterial chemoembolization and its relationship with angiogenesis. Methods 48 rabbits were divided into 4 groups randomly by randomization after intrahepatic tumor implantation for 2 weeks. Different treatments were given via hepatic arterial cannulation. The rats in normal saline group, simple lipiodol group and doxorubicin - lipiodol group Embolization group and As 2 O 3 -iodol embolization group. One week after the treatment, the microvessel density (MVD) in the tumor area was determined by immunohistochemistry. The volume and necrosis of the liver xenograft were measured and measured 3 weeks after the treatment. The incidence of tumor metastasis in the liver, lungs and other organs was observed. Results One week after treatment, the MVD in each group was (21.8 ± 5.3), (23.4 ± 3.9), (22.4 ± 4.50) and (14.3 ± 3.4) / 400 times (F = 11.246, (P <0.05). The tumor volume in each treatment group was (35.5 ± 7.1), (21.2 ± 8.3) and (20.7 ± 9.1) days, respectively, , (11.8 ± 3.7) cm ~ 3 (F = 21.203, P = 0.000). There were statistically significant differences between the simple lipiodol embolization group, the doxorubicin-lipiodol embolization group and the As2O3-lipiodol embolization group (Q = 6.723, 6.940, 11.119, respectively, P <0.05). There was significant difference between As2O3-iodinated oil embolization group and pure iodized oil embolization group and doxorubicin-iodized oil embolization group 4.398,4.178, P <0.05). There was no significant difference in tumor necrosis area between groups (F = 1.284, Jp = 0.292). The number of lung metastasis nodules in As2O3-iodinated oil embolization group was less than that in other groups H = 14.983, P = 0.002). The diameter of nodules was smaller than other groups (F = 4.580, P = 0.007), the difference was statistically significant. Peritoneal metastasis lymph node score showed that as2O3-lipiodol embolization group had less lymph node metastasis than other groups (H = 9.148, P = 0.027). The number of pulmonary metastasis nodules, diameter and lymph node metastasis and tumor microvessel density were positively correlated (P <0.05). Conclusions As2O3-lipiodol combined with transcatheter arterial chemoembolization can inhibit the growth of transplanted hepatic tumor in rabbits and inhibit the metastasis of lung and peritoneal lymph nodes. The mechanism of its inhibition on metastasis may be related to the inhibition of tumor angiogenesis.
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