超声微泡造影剂促进腺病毒载体感染肝细胞的实验研究

目的 探讨超声微泡造影剂促进腺病毒载体感染肝细胞的有效性。方法 将昆明小白鼠分为三组，每组5只，一组经尾静脉输入含腺病毒载体的造影剂1ml，用低频超声波照射至微泡完全消失(约5min)。第二组经尾静脉输入含腺病毒载体的微泡造影剂，不采用超声波照射。第三组既不输入腺病毒载体也不采用超声波照射，用于对照。转基因后第14d，断颈处死小鼠，立即剖腹，取出肝脏，进行冰冻切片，在荧光显微镜下观察肝组织内荧光蛋白表达情况。结果 以超声触发破坏携带腺病毒微泡方式进行感染的小鼠肝脏中，绝大多数肝细胞均有大量荧光素蛋白表达；而单纯静脉注射腺病毒载体小鼠肝脏中，仅见少数肝细胞中有荧光素蛋白的表达；对照组小鼠肝组织中无荧光素蛋白的表达。结论 利用低频超声波在肝脏局部击碎携带腺病毒的微泡造影剂，有效地提高了腺病毒载体在肝细胞的感染率。

Ultrasound Enhancing the Infection Efficiency of Adenoviral Vector into the Intact Hepaocyte

Objective In this study,the feasibility of delivering and enhancing the uptake of adenoviral vector into the intact hepatocyte by using ultrosound(US) facilitation was determined.Methods We used a mouse model to test the ability of US and microbubble echocontrast agents to increase infection of adenoviral vector into hepaocyte. Fifteen male mouse were divided into 3 groups.Continuous wave Doppler US(1.6 MHz for 5min) was applied to the abdomen overlying liver during intravenors injection with a combination of adenoviral vector and microbubble echocontrast agents in the first group. US was not applied to the abdomen overlying liver during intravenors injection with a combination of adenoviral vector and microbubble echocontrast agents in the second group.The third group was used as control group.The infection of adenoviral vector into the intact hepatocyte was measured with GFP expression in the liver by fluorescence microscopy.Results The GFP expression in hepatocyte was markedly increased in the first group.Conclusion These results show a marked increase in hepatocytic adenoviral vector uptake with the administration of US and microbubble echocontrast agents.