高渝,张唯力,黄赤兵,王志刚,冉海涛.超声微泡介导血管内皮生长因子反义寡核苷酸抑制裸鼠膀胱肿瘤[J].中国医学影像技术,2009,25(9):1537~1540
超声微泡介导血管内皮生长因子反义寡核苷酸抑制裸鼠膀胱肿瘤
Vascular endothelial growth factor antisense oligonucleotides inhibition of bladder carcinoma in nude mice mediated by ultrasound microbubble
投稿时间:2009-01-08  修订日期:2009-03-28
DOI:
中文关键词:  超声微泡  血管内皮生长因子  膀胱肿瘤  反义寡核苷酸
英文关键词:Ultrasound microbubbles  Vascular endothelial growth factor  Bladder neoplasms  Antisense oligonucleotides
基金项目:
作者单位E-mail
高渝 第三军医大学第二附属医院泌尿外科,重庆 400037  
张唯力 重庆医科大学附属第二医院泌尿外科,重庆 400010 66zwl@sina.com 
黄赤兵 第三军医大学第二附属医院泌尿外科,重庆 400037  
王志刚 重庆医科大学超声影像学研究所,重庆 400010  
冉海涛 重庆医科大学超声影像学研究所,重庆 400010  
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中文摘要:
      目的 探讨利用超声辐照微泡造影剂介导血管内皮生长因子(VEGF)-反义寡核苷酸(ASODN)对人膀胱癌裸鼠移植瘤的抑制效应。 方法 建立人膀胱癌裸鼠皮下移植瘤模型后,将24只成瘤裸鼠随机分为4组:UM+ASODN组每只裸鼠尾静脉注射微泡造影剂与VEGF-ASODN混合物,并对移植瘤体用超声波进行辐照;脂质体+ASODN组每只裸鼠尾静脉注射VEGF-ASODN与脂质体混合物;UM组每只裸鼠尾静脉注射微泡造影剂并以同样的条件进行体外超声辐照;单纯对照组每只裸鼠尾静脉注射生理盐水,各组处理每隔2 d进行一次,共计5次。观察裸鼠移植瘤生长情况,免疫组化SP法测Ki67、CD34、VEGF的表达,计算微血管密度、细胞增殖指数,TUNEL法测细胞凋亡指数。 结果 UM+ASODN组裸鼠皮下肿瘤生长速度较对照组明显减慢,肿瘤组织VEGF的表达及微血管密度较对照组降低(P<0.05);与对照组相比,UM+ASODN组肿瘤细胞的凋亡增加(P<0.01),而细胞增殖减少(P<0.05)。 结论 超声微泡介导的VEGF-ASODN转染能有效抑制膀胱癌裸鼠皮下移植瘤。
英文摘要:
      Objective To investigate the effect of inhibition of vascular endothelial growth factor (VEGF)-antisense oligonucleotides (ASODN) on human bladder carcinoma in nude mice mediated by ultrasound microbubble. Methods Twenty-four mice were randomly divided into 4 groups (each n=6) when transplantation tumor was established, and different materials were injected into the mice through caudal veins: ①UM+ASODN group: mixture of microbubble and VEGF-ASODN plus ultrasound irradiation of local tumor; ②liposome+ASODN group: mixture of liposome and VEGF-ASODN; ③UM group: microbubble plus local irradiation with the same condition; and ④control group: normal saline. The treatment was performed every 3 d with total 5 times. The volume change of mouse subcutane tumors was observed. The expression of VEGF, CD34 and Ki67 with immunohistochemistry dyeing were evaluated, and the microvessel density (MVD) and cell proliferation index were calculated. TUNEL assay was used to analyze the apoptosis of tumor cells. Results The growth speed of nude mice tumor in UM+ASODN group was obviously slower than that in control group; the expression of VEGF and the MVD in UM+ASODN group was lower than that in control group (P<0.05), while compared with control group, the apoptosis of tumor in UM+ASODN group increased (P<0.01), but the proliferation of tumor in UM+ASODN group decreased (P<0.05). Conclusion VEGF antisense oligonucleotides mediated by ultrasound microbubbe can efficiently inhibit the growth of human bladder carcinoma in nude mice.
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