重组hfgl2-miRNA腺病毒在裸鼠人肝癌模型中的安全性初探

The Safety of Recombinant Adenovirus Mediated Hfgl2-miRNA In HCCLM6 Tumor Xenograft

目的:探讨针对人hfgl2-miRNA的腺病毒颗粒(Ad-hfgl2-miRNA)在裸鼠人肝癌模型中的体内分布及安全性。方法:利用人肝癌细胞系HCCLM6建立裸鼠人肝癌细胞皮下移植瘤模型,每只裸鼠瘤内注射1×10~9 IU的Ad-hfgl2-miRNA,于给药后第1、3、7、9、11、15、19、24天采用qRT-PCR检测Ad-hfgl2-miRNA在裸鼠心、肝、脾、肺、肾、瘤、小肠中的表达,通过检测体内生化指标及组织病理改变,初步评估药物的安全性。结果:Ad-hfgl2-miRNA在裸鼠心、肝、脾、肺、肾、瘤、小肠中均有表达,以心、肝、肾、瘤、小肠表达较强,维持至停药后第24天。各生化指标检测值无明显异常或仅有轻度异常。组织病理学未见明显病理改变。结论:Ad-hfgl2-miRNA在荷瘤裸鼠体内及瘤内能够安全表达,未见有器官损害表现,为今后开展Ad-hfgl2-miRNA的基因治疗奠定了基础。

Objective： To explore the biodistribution and safety of recombinant adenovirus mediated hfgl2-miRNA （Ad-hfgl2-miRNA） in HCCLM6 tumor xenograft. Methods： The xenograft tumor model was established by subcutaneous inoculation with HCCLM6 cells in nude mice, and this was accompanied with intratumoral injection of Ad-hfgl2-miRNA with the dose of 1 × 109 IU per mouse. The expression of Ad- hfgl2-miRNA in heart, liver, spleen, lung, kidney, subcutaneous tumor and small intestine was detected by qRT-PCR at day 1, 3, 7, 9, 11, 15, 19 and 24. The safety of Ad-hfgl2-miRNA was assessed by blood biochemical test and histopathology examination. Results： Ad-hf- gl2-miRNA was expressed in heart, liver, spleen, lung, kidney, subcutaneous tumor and small intestine until day 24, especially in heart, liver, kidney, subcutaneous tumor and small intestine. They were no obvious abnormity or only mild abnorrnity of biochemical parameters. Histopathology was also normal. Conclusion：Ad-hfg12-miRNA expressed safely in vivo and subcutaneous tumor and there were no organ dam- age, which laid foundations for Ad-hfgl2-miRNA gene therapy in the future.