超声微泡靶向增强RNA干扰质粒转染对移植瘤微血管形成和细胞凋亡的影响

摘要

目的 通过超声微泡靶向破坏的方法,选择Survivin作为靶点对短发夹状RNA干扰质粒(pSIREN/S3)进行转染,探讨其对裸鼠移植瘤微血管形成和细胞凋亡的影响.方法 将荷瘤裸鼠分为对照组、超声辐照诱导质粒组及超声微泡靶向破坏诱导质粒组,对组织样本行组织学检查,测定微血管密度(MVD),以末端脱氧核苷酸转移酶标记法(TUNEL)定量检测分析荷瘤裸鼠模型肿瘤组织的凋亡指数(AI).结果 超声微泡靶向破坏诱导质粒组的MVD明显减少,AI明显升高,与对照组及超声辐照诱导质粒组比较,差异均有统计学意义(P＜0.05).结论 超声微泡靶向破坏联合pSIREN/S3质粒敲除Survivin,能使肿瘤组织中血管生成减少,明显诱导细胞凋亡,为恶性肿瘤基因治疗领域的一个新方法.%Objective To investigate the affects of microvessel and apoptosis induction transfected by ultrasound targeted microbubble destruction (UTMD) techniques associated with short hairpin RNA plasmid (pSIREN/S3) techniques in transplanted tumors experiment.Methods Nude mice were randomly arranged into 3 groups: control group,plasmid injection and ultrasound (P+US), P+UTMD group.Histological examinations were evaluated.Microvessel density (MVD) was detected by CD34 protein expressions and apoptotic index (AI) was measured by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).Results Comparing with those in C and P+US groups, MVD decreased significantly, whereas AI increased remarkably (P＜0.05).Conclusions UTMD combined with shRNA technique can induce apoptosis and reduce angiogenesis without causing any apparently adverse effect, representing a new technology in cancer gene therapy.