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目的观察高强度聚焦超声(High-intensity focused ultrasound,HIFU)联合包裹单纯疱疹病毒-胸苷激酶(Herpessimplex virus-thymidine kinase,HSV-TK)的超声微泡(Ultrasound microbubble)治疗对兔VX2肝移植瘤中缺氧诱导因子-1α(Hy-poxia inducible factor-1α,HIF-1α)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)基因表达及微血管密度(Mi-crovascular density,MVD)的影响,并探讨其机制。方法复制兔VX2肝移植瘤模型,建模4周后,将荷瘤兔随机分为4组:对照组(A组),HIFU组(B组),超声辐照载基因微泡组(C组)和HIFU联合超声辐照载基因微泡组(D组)。治疗后两周观察肿瘤大小,免疫组化法检测肿瘤组织中HIF-1α和VEGF蛋白的表达及MVD,Real-time PCR检测肿瘤组织中HIF-1α和VEGF基因mRNA的转录水平。结果治疗后2周,B、C、D组肿瘤组织中HIF-1α、VEGF蛋白表达量,基因mRNA转录水平,MVD及肿瘤体积均明显低于A组(P<0.05),且D组明显低于B组和C组(P<0.05)。结论 HIFU联合包裹HSV-TK基因的超声微泡治疗可抑制肿瘤生长及肿瘤血管新生,降低残余瘤区HIF-1α和VEGF基因的表达,提高HIFU的疗效。
Objective To observe the effect of ultrasound-microbubble combined with high intensity focused ultrasound (HIFU) and herpes simplex virus-thymidine kinase (HSV-TK) Hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) gene expression and the microvascular density (MVD) Explore its mechanism. Methods Rabbit VX2 liver xenograft model was established. After 4 weeks of modeling, the tumor-bearing rabbits were randomly divided into 4 groups: control group (group A), HIFU group (group B), ultrasound- ) And HIFU combined with ultrasound-mediated gene-loaded micro-bubble group (group D). The tumor size was observed two weeks after the treatment. The expression of HIF-1α and VEGF protein in the tumor tissue was detected by immunohistochemistry. The transcription level of HIF-1α and VEGF mRNA in the tumor tissue was detected by MVD and Real-time PCR. Results The expression of HIF-1α, VEGF protein, gene mRNA, MVD and tumor volume in group B, C and D were significantly lower than those in group A (P <0.05), and were significantly lower in group D In group B and group C (P <0.05). Conclusions Ultrasound treatment with HIFU and HSV-TK gene can inhibit the tumor growth and tumor angiogenesis, reduce the expression of HIF-1α and VEGF in the residual tumor area and improve the therapeutic effect of HIFU.