超声靶向微泡介导PEDF质粒转染小鼠肝癌的实验研究

Study on PEDF plasmid mediated by utrasound-targeted microbubble destruction for treatment of hepatocellular carcinoma in nude mice

目的探讨超声靶向微泡介导色素上皮源性因子(PEDF)质粒转染HepG2荷瘤裸鼠的治疗价值。方法建立裸鼠HepG2肝细胞肝癌模型,随机分为5组。Ⅰ组:对照组;Ⅱ:PEDF质粒组;Ⅲ组:PEDF质粒+微泡组;Ⅳ组:微泡+超声辐照组;Ⅴ组:PEDF质粒-微泡+超声辐照组。疗程结束后观察瘤结节的超声造影特征,计算抑瘤率,并检测瘤组织PEDF蛋白表达。应用SPSS软件分析各组间各参数的差异。结果疗程结束后,Ⅴ组瘤结节超声造影增强明显弱于Ⅰ组;Ⅳ组及Ⅴ组抑瘤率明显高于Ⅱ、Ⅲ组;Ⅴ组瘤组织PEDF蛋白表达高于其他各组。结论超声靶向微泡介导PEDF质粒有助于提高质粒转染率,抑制肿瘤血管生成及肿瘤生长,为肝细胞肝癌的治疗提供了一个新的途径。

Objective To explore whether gene transfection of pigment epithelium - derived factor （PEDF） plasmid to HepG2 hepatocel- lular carcinomatous models by ultrasound mediated microbubble destruction could inhibit hepatocellular carcinoma in mice. Methods HepG2 hep- atocellular carcinomatous models were established in thirty five rats. These rats were randomly divided into five groups ： rats in group I （ control group ） were treated with normal saline ; rats in group II were injected with naked plasmid DNA of PEDF ; rats in group ~I received an injection of a mixture of naked plasmid DNA of PEDF and microbubbles ; rats in group IV were injected with microbubbles followed by immediate ultrasound irradiation ; and rats in group V received an injection of a mixture of naked plasmid DNA of PEDF and microbubbles, with exposure to ultrasound immediately. After the treatment, features of contrast enhanced ultrasound image of lesions in each group were observed, the inhibition rates of tumor were calculated, and expression of PEDF protein in lesions was detected. The difference among groups had been analyzed with statistical software. Results After treatment, the enhancement of lesions in group V was weaker than that of group I ; the inhibition rates of tumor in group V and group IV were higher than those of group II and group III ; the expression of PEDF protein in lesions of groupV was significantly higher than those of other four groups （ P 〈 0.01 ）. Conclusion The therapy of PEDF gene combined ultrasound mediated microbubble destruction is helpful for increasing the expression of PEDF protein and inhibition of angiogenesis and development of tumor. This method provides an useful gene therapy for treatment of hepatocellular carcinoma.