摘要
目的 探讨GE7导入系统经动脉灌注将外源性基因导入卵巢肿瘤细胞的有效性及靶向性。方法 以二甲基苯蒽卵巢埋植法,诱发大鼠卵巢肿瘤模型;将β-半乳糖苷酶基因(β—gal)与GE7导入系统构成四元复合物;取模型大鼠15只,随机分为3组,每组5只,分别经卵巢动脉及尾静脉注入不同浓度的四元复合物。72 h后取大鼠的卵巢肿瘤、心、肝、脾、肺及肾脏,以5-溴-4-氯-3-吲哚-β—D半乳糖苷(X-gal)染色,检测β—gal在肿瘤及各个脏器组织中的表达。结果经卵巢动脉灌注浓度为8μg/m1的四元复合物的大鼠的肿瘤组织,被均匀染为深蓝色,肝、脾、肺及肾脏均有不同程度的蓝染,心脏未见染色;经卵巢动脉灌注浓度为4μg/ml的四元复合物的大鼠的肿瘤组织,可见片状蓝染,肝脏仅见少量点状蓝染,其他脏器未见染色;而经尾静脉灌注浓度为8 μg/ml的四元复合物的大鼠,仅在肺脏见少量片状蓝染,肿瘤组织及其他脏器均未见染色。结论GE7导入系统经动脉灌注导入外源基因,具有较高的转导率及器官靶向性,为应用插管方法进行卵巢癌的基因治疗研究,提供了实验依据。
Objective To investigate the efficiency and targeting of the GE7 system mediated gene transfer in the chemically induced ovarian tumor by intraarterial route. Methods Animal models were chemically induced by 7,12-dimethylbenz [ a] anthracene ( DMBA ) . GE7-polylysine/p-galactosidase ( β-gal)/polylysine-HA20 complexes were constructed. Fifteen rats with induced ovarian tumor were divided into three groups, the complexes were injected through ovarian artery and tail vein, respectively. The tumor, heart, liver, spleen, lung and kidney were obtained at 72 h. X-gal staining was used to check expression of β-gal. Results β-gal was expressed strongly and well-distributed in tumor in the first group, and stained blue in the liver, spleen, lung and kidney, but much weaker than that of tumor. In the second group, β-gal was expressed in the tumor,and weakly expressed in the liver, none was detected in the other organs. In the third group β-gal was detected in the lung slightly, none was detected in the tumor and other organs. Conclusions When GE7 complexes were administrated through ovarian artery, the introduced gene expressed preferentially in ovary. This result was the basis of intraarterial administration of therapeutic gene to treat ovarian cancer.
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2004年第5期338-341,F006,共5页
Chinese Journal of Obstetrics and Gynecology
基金
国家自然科学基金资助项目(39800144)
上海市科技启明星基金资助项目(01QB14009)
关键词
卵巢肿瘤
动物模型
B一半乳糖苷酶类
转染
动脉内注射
Ovarian neoplasms
Disease models, animal
beta-galactosidase
Transfection
Injections, intra-arterial
