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

Experimental study on metastasis and correlation of metastasis with angiogenesis of hepatic tumor in rabbits after transcatheter arterial chemoembolization using As_2O_3 and lipiodol

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 investigate the effect of transcatheter arterial chemoembolization （TACE） using As2O3 and Lipiodol on the growth and metastasis of the implanted hepatic tumor in rabbits and the correlation of metastasis with angiogenesis of the residual tumor. Methods Forty-eight New Zealand white rabbits were randomly divided into four groups and VX2 carcinoma was implanted in the left lobes of the rivers. Two weeks later, a catheter was inserted into the hepatic artery and infusion was performed via the hepatic artery using physiological saline （ group A ）, Lipiodol （ group B）, ADM-Lipiedol （ group C ）, and As2O3-Lipiodol （group D）, respectively. One week after the treatment, the value of microvessel density （MVD） of tumors （samples got by biopsy） was examined by immunohistochemistry. Three weeks after the treatment, the volume and necrotic area of the implanted tumor were measured. The metastases in the liver, lungs and other organs were recorded. Results One week after the treatment, the value of MVD of the tumors was （21.8±5.3）, （23.4±3.9）, （22.4±4.5）, and （14.3 ±3.4） /400 power LM （F= 11. 246, P = 0. 000）. Three weeks after the treatment, the mean volume of the implanted tumor was （35.5±7.1）,（21.2±8.3）.（20.7±9.1）,and （11.8±3.7）cm^3（F=21.203,P=0.000） in groups A,B,C and D,respectively.There was significant difference between group D and group B（q=4.398,P〈0.05）,and between group D and group C（q=4.178,P〈0.05）,Meanwhi9le there was significant difference between group B,C,D versus group A（q=6.723,6.940,11.119,P〈0.05）.There was no statistical difference for necrosis area of the tumors（F=1.284.P=0.292）.The number of lung metastatic nodes in group D was less than that in other groups（H=14.983,P=0.002）.and the diameter of lung metaststic nodes in group D was also smaller than that in other gruops（F=4.580.P=0.007）.The score of celiac lymph node metastasis grading in As2O3-Lipiodol treatment group was less than that in other groups（H=9.148,P=0.027）,There was a positive correlation between the number and size of metastasis in lungs and the value of MVD in the tumor area（P〈0.05）,and also between the celiac lymph node metastasis and the value of MVD in the tumor area（P〈0.05）,Conclusion TACE using As2O3 and Lipiodol can inhibit the growth of tumor and decrease tumor metastasis in lungs and celiac lymph node,and the inhibition of the neovascularization may be an important mechanism for inhibiting tumor growth and metastasis.