探讨发卡结构小片段RNA（small hairpin interfering RNA,shRNA）干扰人 ERG（human etherαgogorelated gene，HERG）钾通道治疗裸鼠皮下人成神经细胞移植瘤的疗效和作用机制。方法：用真核转录载体 mU6pro构建针对herg基因的发卡状RNA干扰质粒（shRNAherg）。 18只 BALB/c裸小鼠皮下接种成神经细胞瘤SHSY5Y细胞，建立裸鼠皮下人成神经细胞移植瘤模型，当瘤体积达到100 mm3 时随机分成3组，分别为生理盐水组（Ⅰ）、对照质粒组（Ⅱ）、干扰质粒组（Ⅲ）。各组瘤内分别注射生理盐水、对照质粒、干扰质粒，以后每7 d注射1次，连续15 d。观察各组肿瘤生长情况，RTPCR测定肿瘤组织 herg 基因 mRNA 含量变化，免疫组化检测肿瘤组织中 HERG钾通道蛋白变化。结果： 经治疗后，第Ⅲ组肿瘤生长受到明显抑制，Ⅱ、Ⅲ组抑瘤率分别为3.04%和29.78%（P<0.05）。肿瘤组织内herg 基因 mRNA含量、HERG钾通道蛋白，Ⅲ组较Ⅰ、Ⅱ组表达减弱。结论：构建的shRNA干扰质粒可通过靶向性抑制herg基因及其编码的HERG钾通道蛋白的表达，有效地抑制人成神经细胞瘤的生长。

To explore the therapeutic efficacy and mechanism of shRNA in treatment of subcutaneously implanted SHSY5Y cells in nude mice by interfering human etherαgogorelated gene （HERG）potassium channel expression. Methods: Eukaryotic vector mU6pro was used to construct herg genetargeting small hairpin interfering RNA plasmid: shRNAherg. Eighteen BALB/c nude mice were inoculated with SHSY5Y cells subcutaneously to establish neuroblastoma model. When the implanted tumors grew to about 100 mm3, the mice were divided into randomly 3 groups: Intratumor injection of normal saline (group Ⅰ), shRNAcontrol plasmid (group Ⅱ), and shRNAherg plasmid (group Ⅲ). The injections were given twice at an interval of 7 d after the first injection. The tumor growth was observed; the expression of mRNA and protein of HERG potassium was determined by RTPCR and the immunohistochemical method, respectively. Results: The tumor growth was obviously inhibited in group Ⅲ; the inhibitory rates in groupⅡand group Ⅲ were 3.04% and 29.78%, respectively (P< 0.05). Compared with groupⅠandⅡ, group Ⅲ had lower levels of HERG mRNA and protein after treatment. Conclusion: The constructed shRNA can depress the growth of neuroblastoma by specifically silencing the expression of HERG potassium protein.

国家自然科学基金资助项目（No.3047209,30500620）