CAJ | 학술논문

目的：探讨缺氧诱导因子（HIF1α、HIF2α）在高强度聚焦超声（HIFU）治疗后的残余肿瘤中的变化。方法建立肝癌HpG2细胞株裸鼠移植瘤模型30只，采用CZF-Ⅱ型HIFU治疗仪治疗，随机分为对照组、治疗后1 d、3 d、5 d、1周、2周组。HE染色观察标本病理变化；免疫组化、Western blotting和实时荧光定量PCR技术检测HIF1α、HIF2α蛋白和mRNA水平。结果 HE染色表明治疗后有残余肿瘤细胞和大片坏死区域。免疫组化表明HIF1α、HIF2α蛋白在各组中出现强弱不同表达。Western blotting和RT-PCR显示HIF1α蛋白和mRNA水平在治疗后1~3 d表达逐渐升高，在3 d组达到高峰，与其他组比较有统计学意义（P<0.05），在5 d、1周、2周组逐渐下降。同时，HIF2α蛋白和mRNA在治疗后1 d、3 d组与对照组之间无明显差异（P>0.05），在5 d、1周、2周组表达逐渐升高，与对照组之间有差异（P<0.05）。结论 HIFU治疗后的残余肿瘤，HIF1α、HIF2α在不同时间出现的变化，可能与残癌中发生的细胞凋亡和血管生成有关。
목적：탐토결양유도인자（HIF1α、HIF2α）재고강도취초초성（HIFU）치료후적잔여종류중적변화。방법건립간암HpG2세포주라서이식류모형30지，채용CZF-Ⅱ형HIFU치료의치료，수궤분위대조조、치료후1 d、3 d、5 d、1주、2주조。HE염색관찰표본병리변화；면역조화、Western blotting화실시형광정량PCR기술검측HIF1α、HIF2α단백화mRNA수평。결과 HE염색표명치료후유잔여종류세포화대편배사구역。면역조화표명HIF1α、HIF2α단백재각조중출현강약불동표체。Western blotting화RT-PCR현시HIF1α단백화mRNA수평재치료후1~3 d표체축점승고，재3 d조체도고봉，여기타조비교유통계학의의（P<0.05），재5 d、1주、2주조축점하강。동시，HIF2α단백화mRNA재치료후1 d、3 d조여대조조지간무명현차이（P>0.05），재5 d、1주、2주조표체축점승고，여대조조지간유차이（P<0.05）。결론 HIFU치료후적잔여종류，HIF1α、HIF2α재불동시간출현적변화，가능여잔암중발생적세포조망화혈관생성유관。
Objective To study the changes in hypoxia-inducible factor (HIF1α, HIF2α) in the residual tumor cells in nude mice bearing hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU). Methods Thirty nude mice bearing human HCC received treatment with HIFU. At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the mice were examined for pathological changes of the residual tumor with HE staining; SP immunohistochemistry, Western blotting and real-time quantitative PCR were used to detect the protein and mRNA expressions of HIF1α and HIF2α in the tumor. Results HE staining revealed the presence of residual tumor cells and large necrotic areas after the treatment. Immunohistochemistry showed a gradual increment of HIF1αprotein and mRNA expressions after the treatment, reaching the peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and 1 and 2 weeks. HIF2αexpressions at either the protein or mRNA levels exhibited no significant changes within 3 days after the treatment (P>0.05) but increased significantly at 5 days and 1 and 2 weeks (P<0.05). Conclusion The changes of HIF1αand HIF2αin the residual tumor after HIFU treatment in nude mice bearing HCC can be associated with tumor cell apoptosis and angiogenesis after the treatment.