超声引导下瘤体内注入超声造影剂和P53基因治疗大鼠肝癌的初步研究

目的　探讨超声引导下将超声造影剂和人野生型 p5 3基因直接注入瘤体内对大鼠肝癌基因表达的影响。方法　采用免疫抑制法建立大鼠原位肝癌模型。 2 4只实验Wistar大鼠随机分成 4组。第 1组 :超声引导下将基因直接注入瘤体内并不用超声照射 ;第 2组 :注入基因后用超声照射瘤体 ;第 3组 :注入造影剂和p5 3基因后不行超声照射 ;第 4组 :用超声照射注入造影剂和基因的瘤体。 48h后用半定量逆转录 聚合酶链式反应 (RT PCR)测定肝癌细胞内 p5 3mRNA的表达情况。 结果　超声引导下可准确地将基因注入肝癌内 ,4组肝癌细胞内均有 p5 3mRNA的表达 ,第 4组的表达量最高 ,明显高于其他三组 ( P <0 .0 0 1)。第 2组的基因表达量次之 ,高于另外两组 (P <0 .0 5 )。第 1、3组间在外源基因表达上的差异没有显著性意义 (P >0 .0 5 )。结论　超声引导下瘤体内注射超声造影剂和p5 3基因后用超声照射 ,既可有效地控制肝癌基因治疗的靶向性 ,又能提高外源基因的表达量。

Preliminary study on therapy of liver cancer in rats using ultrasound-guided intertumoral injection of human wild-type p53 plasmid by means of ultrasound with echo contrast agent

Objective To assess the effect of echo contrast agent and human wild-type p53 plasmid on gene expression of liver cancer in rats by ultrasound-guided directly intratumoral injection. Methods A rat liver cancer model in situ was established by immunosuppression. Twenty-four Wistar rats were divided into 4 groups. p53 plasmid was ultrasound-guided directly injected into liver cancer without ultrasound exposure in group 1 and with that in group 2. Followed by injection of p53 and echo contrast agent the liver cancer was not irradiated by ultrasound in group 3 and was done in group 4. Semiquantitative RT-PCR was used to detect wild-type p53 mRNA expression after 48 hours. Results Gene could be injected exactly into the liver cancer with ultrasound intervention,and expression of p53 mRNA was found in all 4 groups. Expression in group 4 was significantly higher than others( P < 0.001 ),that in group 2 took second place,and there was no difference in group 1 and 3( P > 0.05 ). Conclusions Ultrasound-guided directly injection of echo contrast agent and p53 plasmid followed by ultrasound exposure could either determine targeted gene therapy of liver cancer or enhance the expression of the exogenous gene.