目的:经Beagle犬肝脏血管注射重组腺病毒介导反义c—myc基因(Ad-ASmye)载体,观测其体内分布及毒副作用,以评价Ad-ASmye治疗肝癌的临床前期安全性。方法:选择4只体重8-10 kg健康Beagle犬,全麻后开腹,经肝动脉或门静脉注射Ad-ASmyc,注射Ad-ASmye前及注射后第3,7,14,21天取肝组织及抽取静脉血化验,PCR检测Ad-ASmyc在各器官组织中的分布,常规切片观察各器官病理变化,ELISA方法检测血中抗腺病毒抗体的产生。结果:经Beagle犬肝脏血管注射后,Ad-ASmyc可持续转导正常肝细胞达3周,实验犬一般情况好,血、肝、肾功能无明显异常,在肝脏、脾脏、肾脏、胃、心脏、皮肤中可检测到重组腺病毒的分布,镜下可见Ad-ASmyc剂量依赖性的肝组织轻微的炎症反应,注射后7 d血中有抗腺病毒载体的抗体产生,14 d达高峰,21 d开始下降。结论:经Beagle犬肝动脉或门静脉途径注射Ad—ASmyc均可转导至肝细胞,Ad-AS-myc对实验犬的毒副作用较轻。 OBJECTIVE: To evaluate the clinical preclinical safety of Ad-ASmye in the treatment of hepatocellular carcinoma by injecting the recombinant adenovirus-mediated antisense c-myc gene (Ad-ASmye) into the liver of Beagle dogs and observing its distribution in vivo and its toxicities and side effects. Methods: Four healthy Beagle dogs weighing 8-10 kg were selected. After general anesthesia, they were given laparotomy. Ad-ASmyc was injected into hepatic artery or portal vein, and before and after Ad-ASmye injection, liver tissue was taken on the 3rd, 7th, 14th and 21st day after injection The venous blood samples were collected and the distribution of Ad-ASmyc in various organs was detected by PCR. Pathological changes of organs were observed by routine sections and the anti-adenovirus antibodies were detected by ELISA. Results: After being injected into the liver of Beagle dogs, Ad-ASmyc could transduce the normal hepatocytes continuously for 3 weeks. The dogs in normal condition had good blood, liver, and kidney function. There was no obvious abnormality in the liver, spleen, kidney, stomach, heart , The distribution of recombinant adenovirus could be detected in the skin. Ad-ASmyc showed a slight inflammatory reaction in a dose-dependent manner in the liver microscopically. Anti-Adenovirus antibody was produced in the blood on day 7 after injection, reaching a peak on day 14 d began to decline. Conclusion: Ad-ASmyc can be transduced into hepatocytes via the hepatic artery or portal vein of Beagle dogs. Ad-AS-myc has less toxic side effects on experimental dogs.