rAAV-shRNA-CDK2对肝癌人肝癌裸鼠血液系统的影响

目的:探讨新型基因药物rAAV-shRNA-CDK2对人肝癌裸鼠血液系统的影响,评估其安全性。方法:采用皮下接种人肝癌Hep G2细胞构建荷瘤裸鼠,10天后将其随机分为3组:肿瘤组、NC组及rAAV-shRNA-CDK2组,每组雌雄裸鼠各6只。通过尾静脉注射定量给药,15天后取眼球血并处死裸鼠。检测血常规指标和骨髓细胞周期。结果:所有裸鼠平均血小板体积略高于该周龄鼠的正常值范围,但各组间比较差异无统计学意义(P0.05);肿瘤组雌性裸鼠的中性粒细胞百分比显著高于rAAV-shRNA-CDK2组,而淋巴细胞百分比明显低于rAAV-shRNA-CDK2组(P0.05),但指标数值均在正常值范围内。各组雄性裸鼠骨髓细胞周期分布比较差异均无统计学意义(P0.05),而肿瘤组雌性裸鼠骨髓细胞G2/M期比例明显高于rAAV-shRNA-CDK2(P0.05),但两组其他周期骨髓细胞比例比较差异无统计学意义(P0.05)。结论:rAAV--shRNA-CDK2并未对人肝癌裸鼠血液系统产生不良影响。

Effects of rAAV-shRNA-CDK2 on the Blood System of Nude Mouse Model of Human Liver Cancer

ABSTRACT Objective: To investigate the effects of novel gene drugs rAAV-shRNA-CDK2 on the blood system of nude mice with hepatocellular carcinoma (HCC) and evaluate its safety. Methods: To construct tumor bearing nude mice, human hepatoma HepG2 cells were subcutaneously vaccinated into nude mice, they were randomly divided into 3 groups after 10 days: tumor group, NC group and rAAV-shRNA-CDK2 group. 6 males and females in each group were quantitatively administered by tail vein. 15 days later, the eyeball blood was taken and nude mice were killed. The blood routine index and bone marrow cell cycle were detected. Results: The mean platelet volume of all mice was slightly higher than the normal range of values of mice with the same age, but there was no significant difference between the groups(P>0.05). The percentage of neutrophils in the femal nude mice of tumor group was significantly higher than that in the rAAV-shRNA-CDK2 group, while the percentage of lymphocytes was significantly lower than that in the rAAV-shRNA-CDK2 group (P<0.05), but the index values were in the normal range. The bone marrow cell cycle distribution of male nude mice in each group showed no significant difference (P > 0.05); bone marrow cells in G2/M phase of female nude mice in the tumor group was significantly higher than that of the rAAV-shRNA-CDK2 group(P<0.05), but there was no significant difference in other two cycles of bone marrow cells proportion between two groups(P>0.05)(P>0.05). Conclusion: rAAV--shRNA-CDK2 had no significantly detrimental effect on the blood system of nude mice with human liver cancer.