纳米荧光探针在大鼠肝癌血供分子影像中的应用

Application of nano-fluorescent probe in blood supply molecular imaging of hepatocellular carcinoma model in rats

目的探讨纳米荧光探针在大鼠肝癌血供分子影像中的应用,为肝癌的双血供治疗奠定基础。方法通过二乙基亚硝胺化学诱导法建立12只大鼠肝硬化肝癌模型,15周时行磁共振扫描、切取肝组织行病理切片;通过肝动脉和门静脉应用不同的纳米荧光探针,观测肝癌组织血供的分子影像,组间比较采用两样本均数的t检验。结果12只大鼠13~14周时死亡4只,15周时存活率为66.67%,成瘤率100%。病理切片符合肝细胞性肝癌征象;分子荧光成像在动脉时癌结节5,6-二氯-3,4-二氢-2(1H)-亚胺喹唑啉-3-乙酸乙酯氢溴酸盐(DiI)荧光强度[(2.99±0.41)×10^(7)]高于周围肝组织[(1.06±0.22)×10^(7),t=-9.410,P<0.05];而在门静脉时癌结节Alexa fluor 647荧光强度[(1.30±0.29)×10^(7)]低于周围肝组织[(2.76±0.38)×10^(7),t=7.480,P<0.05],两者差异均有统计学意义。肝癌玻片扫描提示肝癌结节动脉血供高于周围肝组织,而肝癌结节实质及周围均存在门静脉供血,以周围为著。结论二乙基亚硝胺诱导法可建立成熟稳定的肝硬化肝癌模型,纳米荧光探针在微观水平观测到肝癌组织为动静脉复合血供。

Objective To investigate the application of nano-fluorescent probes in hepatocellular carcinoma(HCC)blood supply molecular imaging in rats and pave the foundation of double blood supply treatment in HCC.Methods The HCC models of 12 rats were established by diethylnitrosamine(DEN)chemical induction.After 15 weeks,the magnetic resonance imaging(MRI)and pathological findings were observed.Different nano-fluorescent probes were applied through hepatic artery and portal vein to observe the blood supply molecular images of HCC tissues.Results A total of 4 rats died at 13-14 weeks,with a survival rate of 66.67%at 15 weeks and the tumor formation rate of 100%.The pathological sections were consistent with the signs of HCC.The arterial 1,1′-dioctadecy1-3,3,3′,3′-tetramethylindocarbocyanine perchlorate(DiI)fluorescence intensity in tumor of molecular fluorescence imaging[(2.99±0.41)×10^(7)]was significantly greater than the surrounding liver tissue[(1.06±0.22)×10^(7),t=-9.410,P<0.05];and fluorescence intensity of Alexa fluor 647 in tumor of portal vein[(1.30±0.29)×10^(7)]was significantly weaker than that of peripheral liver tissue[(2.76±0.38)×10^(7),t=7.480,P<0.05].The slide scan showed that arterial blood supply in tumor tissue was higher than the surrounding liver tissue,and the portal vein blood supply was found in the parenchyma and surrounding areas of the liver tumor.Conclusion The DEN induction is a mature and stable method to establish the HCC model,and the nano-fluorescent probe can observe the double blood supply for HCC in the microscopic level.