siRNA沉默HIF-1α基因联合经导管动脉栓塞术对兔VX2肝癌模型疗效及微循环的影响  

Therapeutic effect of hypoxia inducible factor-1αcombined with transcatheter arterial embolization on rabbit VX2 liver tumor model

作　　者：戴琦 刘日 闫昆 郑建军 张景峰 DAI Qi;LIU Ri;YAN Kun;ZHENG Jian-jun;ZHANG Jing-feng(Department of Radiology,Hwa Mei Hospital,University of Chinese Academy of Sciences,Zhejiang 315010,China)

机构地区：[1]中国科学院大学宁波华美医院放射科,浙江宁波315010 [2]中国科学院大学宁波生命与健康产业研究院,浙江宁波315010 [3]浙江大学医学院附属第一医院放射科,浙江杭州310003

出　　处：《影像诊断与介入放射学》2020年第5期361-367,共7页Diagnostic Imaging & Interventional Radiology

基　　金：浙江省自然科学基金(LY18H180004);浙江省医药卫生科技计划项目(2017KY138);宁波市自然基金(2016A610137)。

摘　　要：目的探讨小干扰核糖核酸(siRNA)沉默缺氧诱导因子-1(HIF-1α)基因联合经导管动脉栓塞术(TAE)治疗对兔VX2肝肿瘤模型疗效及微循环的影响。方法24只VX2肝癌模型兔随机分为4组,每组6只。各组于介入治疗当天(VX2肿瘤种植第14天)随机选取3只处死,余下3只进行介入治疗。A组:肝动脉内注入PVA微粒与对比剂混悬液;B组:肝动脉内灌注HIF-1α-shRNA溶液;C组:肝动脉内灌注PVA微粒与对比剂混悬液及HIF-1α-shRNA溶液;D组:对照组,肝动脉内灌注生理盐水。介入治疗后第14天处死各组余下的模型兔。取VX2肿瘤样本行病理学与免疫组织化学检查、实时定量PCR分析。观察各组VX2肿瘤组织HIF-1α和血管内皮生长因子(VEGF)的蛋白表达、HIF-1α和VEGF的mRNA表达水平。结果VX2肿瘤组织HE染色显示TAE组、HIF-1α-shRNA组、TAE+HIF-1α-shRNA组和对照组的核分裂象计数分别为11.33±3.51、13.42±3.96、7.33±2.31和20.50±4.18。与对照组、TAE组、HIF-1α-shRNA组相比,TAE+HIF-1α-shRNA组能显著抑制HIF-1α和VEGF的蛋白表达(PHIF-1α<0.001;PVEGF<0.001)。实时定量PCR结果表明,TAE+HIF-1α-shRNA组的HIF-1α、VEGF的mRNA表达水平明显低于其余各组(P<0.001)。结论TAE联合RNA干扰HIF-1α可抑制TAE后的HIF-1α、VEGF的mRNA表达,减少肿瘤血管生成,其治疗效果优于单纯TAE治疗。Objective To investigate the therapeutic effect of hypoxia inducible factor-1α(HIF-1α)combined with transcatheter arterial embolization(TAE)on rabbit VX2 liver tumor model.Methods Twenty-four VX2 liver cancer model rabbits were randomly divided into 4 groups of 6 each.On the 14th day of VX2 tumor implantation,3 rats were randomly selected and executed in each group,and the remaining 3 rats underwent interventional therapy on the same day.In group A,the PVA particles and contrast agent suspension were injected into the hepatic artery.In group B,the HIF-1α-shRNA solution was injected into the hepatic artery.In group C,the PVA particles and contrast medium suspension as well as HIF-1α-shRNA solution were injected into the hepatic artery.In group D as control group,the hepatic artery was injected with normal saline.The rabbits in each group were killed on the 14th day after interventional therapy.The expression levels of mRNA and protein were detected using the real-time reverse transcription polymerase chain reaction(RT-PCR)and immunohistochemistry assays.Results The H&E staining showed mitotic figures of 11.33±3.51 in the TAE group,13.42±3.96 in the HIF-1α-shRNA group,7.33±2.31 in the TAE+HIF-1α-shRNA group and 20.50±4.18 in the control group.Compared with the control,TAE,and HIF-1α-shRNA groups,the TAE+HIF-1α-shRNA group significantly inhibited the protein expression of HIF-1αand VEGF(PHIF-1α<0.001;PVEGF<0.001).The immunohistochemical staining and RT-PCR assay showed that the expression levels of HIF-1αand VEGF in TAE+HIF-1α-shRNA group were both significantly lower than those in other groups(P<0.001).Conclusion HIF-1α-shRNA improves therapeutic effect of TAE by inhibiting expressions of HIF-1αand VEGF on rabbit VX2 liver tumor model.

关 键 词：低氧诱导因子-1α 小干扰核糖核酸 兔 肝脏 VX2肿瘤 经导管血管栓塞术 

分 类 号：R735.7[医药卫生—肿瘤]