制备载双歧杆菌胞外多糖纳米粒子（ Bifidobacterium exopolysaccharide loaded nanoparticles， B. EPS NPs)，探讨 B. EPS NPs对人胃癌细胞裸鼠移植瘤增殖和凋亡的影响。方法：取Fe3O4纳米粒子和 B. EPS，采用乳化高温固化法制备 B. EPS NPs。建立人源胃癌细胞(BGC 823)裸鼠移植瘤模型，接种6 d后随机分为5组，分别以生理盐水、NPs、环磷酰胺 （cytoxan,CTX） 、游离 B. EPS及 B. EPS NPs进行灌胃治疗。观察各组瘤体的生长情况，TUNEL法检测细胞凋亡，透射电镜观察细胞超微结构，免疫组化法检测增殖细胞核抗原(proliferating cell nuclear antigen，PCNA)及凋亡调控基因bcl 2、bax蛋白表达水平。结果：空载NPs和 B. EPS NPs平均粒径分别为（560±21）nm、（960±32）nm， B. EPS NPs载药率为30％。 B. EPS NPs对移植瘤的抑瘤率为（46.4±2.94）%，高于游离 B. EPS组的(32.0±1.62)％和NPs组的(4.9±0.98)％。 B. EPS NPs组移植瘤细胞凋亡指数明显高于 B. EPS组\[（66.8±5.58）％ vs （41.3±4.26）％\]（ P <0 .01)。透射电镜观察到 B. EPS NPs治疗后的移植瘤细胞核染色质凝集成块状，出现了典型的凋亡特征。与 B. EPS相比， B. EPS NPs组PCNA及bcl 2的表达水平有所降低（ P <0.01），bax的表达水平有所提高（ P <0 .01）。结论：纳米粒子运载 B. EPS增强了后者对胃癌细胞(BGC 823)移植瘤的增殖抑制作用和促凋亡作用，提高了 B. EPS的抗肿瘤活性。

To prepare Bifidobacterium exopolysaccharide loaded nanoparticles（ B. EPS NPs）and to investigate the effect of B. EPS NPs on the proliferation and apoptosis of human gastric cancer cells transplanted in nude mice. Methods: B. EPS and nanoparticles of Fe3O4 were used to prepare B. EPS NPs by the method of emulsion polymerization. Transplant models of human gastric cancer cells BGC 823 were established in nude mice and were divided into 5 groups after 6 days, namely, the normal saline group, nanoparticle group(NPs), cytoxan (CTX) group, B. EPS group, and B. EPS NPs group. The corresponding agents were used for gastric lavage. The growth of tumor was observed and cell apoptosis was detected by TUNEL. The ultra microstructure of tumor cells was observed under TEM, expression of proli ferating cell nuclear antigen (PCNA), bcl 2 and bax was examined by immunohistochemistry method. Results: The diameters of the empty loaded NPs and B. EPS NPs were (560±21）nm and （960±32）nm, respectively; the drug loading capacity of B. EPS was 30%. The growth of the transplanted tumor was inhibited in B. EPS NPs group, with the inhibitory rate being （46.4±2.94）%, which was higher than that of the B. EPS group(\[320±1.62\]％) and NPs group \[(4.9±0.98\]％). The apoptosis index in B. EPS NPs group (\[66.8±5.58\]％) was significantly higher than that of the B. EPS group（ \[41.3±4.26\]％, P <001）. TEM showed typical apoptotic structures in B. EPS NPs group. Compared with B. EPS group， B. EPS NPs group had markedly lower expression of PCNA and bcl 2 ( P <001) and higher expression of bax ( P <0.01). Conclusion: Nanoparticles can enhance the inhibitory effect and pro apoptosis effect of B. EPS for human gastric cancer (BGC 823) transplanted tumor.

国家自然科学基金资助项目(No.30371055)