中文摘要：

目的 探讨羟基磷灰石纳米粒子（NanoHAP）在体内对兔VX2肝种植瘤生长的抑制作用及对肿瘤细胞bax／bcl-2凋亡蛋白表达的影响。方法 将56只VX2肝荷瘤兔随机分成四组，通过肝动脉灌注NanoHAP溶胶、5-Fu以及5-Fu与NanoHAP的混合液，并与生理盐水组对照。观察各组动物的一般情况，对肿瘤体积进行监测并比较。采用免疫组织化学染色观察bax／bcl-2蛋白的表达。结果 各治疗组对肿瘤生长都有明显的抑制作用。NanoHAP溶胶组肿瘤体积明显小于对照组（P〈0．05），肿瘤生长抑制率达到28．1％；5-Fu组抑瘤率达到43．7％，但动物表现出明显毒副作用；联合治疗组抑瘤率达到51．2％，而且毒副反应明显小于5-Fu组。NanoHAP组及联合治疗组免疫组织化学染色显示bcl-2蛋白表达率分别为41．7％（5／12）、38．5％（5／13），较对照组72．7％（8／11）明显降低；bax蛋白表达率为50．0％（6／12）、61．5％（8／13），明显高于对照组127．3％（3／11）。结论 NanoHAP在体内对兔VX2肝种植瘤生长有明显的抑制作用，而且能明显降低5-Fu的毒性作用。其抑瘤机制可能是通过影响bax／bcl-2的表达加速肿瘤细胞凋亡。

英文摘要：

Objective To evaluate the antitumor effects and the influence on the expression level of bax/bcl-2 genes of the hydroxyapatite nanoparticles in rabbit VX2 transplanted hepatoma. Methods 56 VX-2 transplanted hepatic carcinoma models in rabbit were established and divided into 4 groups at random, 14 rabbits in each group. The rabbits were treated by hepatic artery injection at the 20th day after administration of 4 medicines ： group A, injecting sodium chloride ; group B, injecting hydroxyapatite nanoparticles collosol;group C,injecting 5-Fu;group D,injecting the medicine mixed by hydroxyapatite nanoparticles collosol and 5-Fu. The hepatic artery was blockaded. The changes in the rabbits were observed and the size of the tumor was recorded. The HE and immunohistochemical double staining techniques were used to detect the expression of the two genes （bcl-2/bax） in the tumors. Results Hydroxyapatite nanopartieles could inhibit the growth of tumor with the inhibition rate being 28.1%. The size of tumors in group B was significantly smaller than in control group （ P 〈 0.05 ）. In group D, the inhibition rate was 51.2% and the side effect was less than in group C. The positive expression rate of bcl-2 was 41.7% （5/12） in group B and 38.5% （5/13） in group D respectively,which was significantly decreased as compared with group A （72.7% ,8/11）. And the expression rate of bax protein in groups B and D was 50.0% （6/12） and 61.5% （8/13） respectively,which was significantly increased as compared with group A （27.3% ,3/ 11 ）. Conclusion Hydroxyapatite nanoparticle can decrease the expression of bcl-2 gene and increase the expression of bax gene. It can inhibit the growth of the VX-2 transplanted hepatic carcinoma in rabbits in vivo by inducing the apoptosis.