可显影硫酸钡海藻酸钠微球介入治疗兔VX2肝肿瘤

Alginate-barium sulfate microspheres via vascular interventional procedures in treatment of VX2 tumor-bearing rabbits

目的:研究硫酸钡海藻酸钠微球对兔VX2肝肿瘤的介入治疗作用。方法:新西兰兔24只,随机分为3组:正常对照组(A组,n=5)、肿瘤对照组(B组,n=10)和介入治疗组(C组,n=9)。介入治疗模拟人肝动脉插管方法。A、B、C组于介入术后7d行肝功能检查,B组、C组各5只动物于介入术后2周观察肿瘤质量、体积,并行病理学检查,包括常规H-E染色、CD34及VEGF免疫组化检测;B组5只、C组4只动物观察生存期。结果:介入治疗后7d,丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平B、C组均高于A组(P<0.01),但C组ALT、AST数值低于B组(P<0.01)。C组肿瘤质量(2.434±0.992)g,B组(4.696±1.246)g,差异具有统计学意义(P<0.01)。C组肿瘤体积(2.126±0.929)cm3,B组(3.962±1.101)cm3,差异具有统计学意义(P<0.01)。病理学检查结果显示C组癌细胞大片坏死,CD34染色大片坏死区无微血管,残存的癌组织内新生血管明显减少,VEGF表达仅见残存的癌细胞胞质呈弱阳性表达;而B组癌巢大,癌细胞丰富,CD34染色可见丰富的新生血管,癌细胞胞质可见丰富的VEGF表达。C组生存期明显延长。结论:硫酸钡海藻酸钠微球介入治疗兔VX2肝肿瘤安全可行;能明显抑制肿瘤生长,且对正常肝组织损伤小,能延长实验兔生存时间。

Objective： To study the therapeutic effect of arterial infusion in treatment of liver VX2 tumors in rabbits. alginate-barium sulfate microspheres via transcatheter hepatic Methods： A total of 24 rabbits were randomly divided into 3 groups, with 5 rabbits in group A （normal control group）; 19 rabbits implanted with liver VX2 tumors were further divided into 2 groups, with 10 rabbits in group B （tumor control group）, and 9 in group C （therapy group）. Rabbits in group C were catheterized with 3F microcatheter by Seldinger technique for interventional therapy. Spiral CT scanning was performed in group B and group C 14 days after implantation and 14 days after treatment. Liver function tests （TB, ALT, and AST） were performed before and 7 days after treatment. Five rabbits in group B and C were sacrificed, to measure the tumor weight and volume; MVD and expression of CD34 and VEGF expression were examined by immunohistochemical technique. Survival periods of the animals were observed and animals were sacrificed 70 days after treatment. Results： Seven days after treatment, the ALT and AST in group B were significantly higher than those in group A and group C （P〈0.01）. Fourteen days after treatment, the average tumor weights in group C was significantly lower than that in group B （[2. 434±. 992] g vs [4. 696±1. 246] g, P〈0.01） ; and the tumor volume in group C was also significantly lower than that in group B （ [2. 126±0. 929] cma vs [3. 962 ±1. 101]cm3, P〈0. 01）. Pathological examination showed large necrotic areas in the tumors in group C. CD34 stained necrotic area had no obvious mierovessels. The angiogenesis was decreased greatly in the tumor tissues left. Weak VEGF expression was only found in the survived tumor cells. In contrast, group B had abundant cancer cells, large cancerous nests, abundant CD34 positive angiogenesis and strong cytoplasmic staining of VEGF. The survival of rabbits in group C was obviously longer than in group B. Conclusion： Treatment with alginate-barium sulfate microsphere via hepatic artery infusion is safe and feasible for treating liver VX2 tumor. Alginate-barium sulfate microspheres can obviously inhibit tumor growth and have less toxicity to the normal liver tissue.