目的: 探讨缺氧诱导因子1α（hypoxia inducible factor 1α，HIF1α）特异性siRNA调节肿瘤组织乏氧状态的抗肿瘤效应。方法：构建含有HIF1α特异性RNAi序列的重组腺病毒载体，建立携带VX2肿瘤细胞的荷瘤模型兔。将构建好的重组腺病毒载体注入兔耳缘静脉中进行治疗，以注入无干扰序列腺病毒载体为对照。采用正电子发射计算机断层显像(positron emission computed tomography, PET)成像的方法观察模型兔肿瘤组织乏氧和坏死的变化。切除剥离肿瘤，测量肿瘤体积；HE染色法检测肿瘤组织坏死程度；采用RTPCR检测HIF1α在肿瘤组织中表达的变化。结果：成功构建携HIF1α特异性siRNA的重组腺病毒，其滴度约为1.1×1010 PFU/ml。PET成像检测显示，经siRNA重组腺病毒治疗后的移植瘤组织中18FFDG标准摄取率（SUV）较对照兔显著降低\[(3.51±0.36)％ vs (8.73±0.83)％ ，P<0.01\]，图像显示肿瘤组织内部出现了明显的缺氧和坏死区域。HIF1α siRNA治疗组的移植瘤体积显著小于对照组(P<0.01)，肿瘤组织坏死面积明显大于对照组(P<0.01)；RTPCR检测显示，治疗组肿瘤组织中HIF1α mRNA 水平显著低于对照组(P<0.01)。结论：HIF1α特异性siRNA使肿瘤组织HIF1α表达减少、肿瘤组织乏氧加剧和坏死增加，从而产生明显的抗肿瘤效应。

Objective:To explore the antitumor and hypoxia regulatory effect of HIF1α siRNA in tumor tissues. Methods:The HIF1α siRNA adenovirus vectors targeting HIF1α were constructed and the rabbit VX2 tumor model was established. The constructed vectors were injected into rabbits through ear vein; noninterference sequence was injected as control. PET (positron emission computed tomography) was used to observe the changes of hypoxia and necrosis in tumor tissues. The tumors were removed and the tumor volumes were measured. HE staining was used to observe the degree of the necrosis; RTPCR was used to detect the change of HIF1α expression in tumor tissues. Results: The recombinant HIF1α siRNA adenovirus vectors were successfully constructed, with a titre of 1.1×1010 pfu/mL. PET imaging showed that the SUV of 18FFDG was significantly decreased in HIF1α siRNA injected group than that in the control group (\[351±0.36\]％ vs \[8.73±0.83\]％, P<0.01). Images showed that the tumor tissue had obvious hypoxia and necrosis. The sizes of the tumors of HIF1α siRNA injected group were significantly smaller than that of the control group (P<0.01); the necrosis areas in the tumors of HIF1α siRNA injected group were significantly larger than that of control group (P<0.01). RTPCR demonstrated that the expression of HIF1α mRNA in HIF1α siRNA injected group was significantly lower than that in the control group (P<0.01). Conclusion: HIF1α specific siRNA can reduce HIF1α expression in tumor tissues and aggregate the hypoxia and necrosis of tumor tissue, therefore producing obvious antitumor effect.

山东省科技厅博士基金项目，（No. 2006BS03035）。