乳腺癌小鼠体内应用生孢梭菌方式及细菌分布方式-第三军医大学学报.docVIP

生孢梭菌在小鼠乳腺癌靶向治疗中的应用研究 苏昊1，张艳丽2，胡昊宇1，马瑞华1，张伟伟1，袁欣欣1 (266071 青岛，青岛大学医学院临床医学专业1， 青岛大学医学院病原生物学实验室2) [摘要] 目的 观察生孢梭菌在乳腺癌小鼠体内的动态分布及安全性;为实体瘤治疗中生孢梭菌的具体应用提供参考。方法 制备小鼠EMT6乳腺癌模型；培养生孢梭菌的芽胞和繁殖体，分别采用尾静脉和瘤内注射两种方式注射到乳腺癌小鼠体内，定期随机选取小鼠，取其肝、肾、脾等重要器官以及肿瘤组织印片，经革兰氏染色后镜下观察组织内细菌分布情况。结果 生孢梭菌的繁殖体与芽胞一样可以选择性的在缺氧的乳腺癌内部定居繁殖，且对小鼠的生命及生存期没有影响；静脉注射和瘤内注射的结果一致，生孢梭菌只在肿瘤内生长，不侵犯正常组织；生孢梭菌在肿瘤消退之前被中性粒细胞吞噬消除。结论 生孢梭菌是一种靶向性好，安全性高，自限性的实体瘤治疗的靶向载体；可以采用静脉注射的方式，利用生孢梭菌的繁殖体、芽胞或二者混合物作为载体携带抗肿瘤基因进行实体瘤的靶向治疗。 [关键词] 生孢梭菌；繁殖体；芽胞；乳腺癌；尾静脉注射；瘤内注射 中图分类号 【Q93-337】文献标识码【A】 Research on the application of Clostridium sporogenes in targeted therapy of mice breast cancer Su Hao 1 ，Zhang Yanli 2, Hu Haoyu 1, Ma Ruihua 1 , Zhang Weiwei 1, Yuan Xinxin 1 (Clinical Medicine, Qingdao University MedicalCollege, Qingdao1， 基金项目：山东省自然科学基金项目（ZR2012HQ005）；山东省医药卫生科技发展计划（2009HD005）；青岛大学2011年创新型教学实验室研究项目；青岛大学医学院2012年度本科生基础医学创新实验项目 作者简介：苏昊(1992-),男，山东郯城人，本科生在读，主要研究方向为乳腺癌的生物治疗。联系方式Email：164296114@ 通讯作者：张艳丽，电话：0532Email：qdzhangyanli1974@163.com Laorabtory of Pathogenic Biology2 , 266071 ，China) Abstract: Objective Our aim is to observe dynamic distribution and safety of Clostridium sporogenes in breast cancer-bearing mice sporogenes of different growth states into the mice in different ways, to provide e for actual applications of Clostridium sporogenes in solid tumors treatment.Methods We prepared EMT6 mice breast cancer models, then injected vegetative forms or spores of Clostridium sporogenes into the tumor-bearing mice by caudal vein and intratumoral injection respectively. We selected a mouse from different groups randomly and periodically to make tissues imprint of their liver, kidney, spleen and tumor ,then made Gram stain slides and observed under a microscope to find the bacteria distribution. Results Clostridium sporogenes vegetative forms just the same as its spores could settle and propagate in the hypoxic breast cancer and had no side-effect on mices life time; the results of intravenous injection were just t