CAJ | 학술논문

目的：探讨基于Reference-Region模型的DCE-MRI 评价恩度对兔VX2骨肿瘤抗血管生成疗效的可行性。方法：将成功建立胫骨VX2肿瘤模型（软组织肿块直径＞1．0 cm）的20只兔子随机分成对照组（n＝10）和实验组（n＝10），分别于给药前、连续给药14天后（对照组药物为生理盐水；实验组药物为恩度，药物浓度为1．5 mg／8 mL）行DCE-MRI扫描，使用Referrence Region模型获得肿瘤组织的对比剂容积转移常量Ktrans和反流速率常数Kep。于第14天扫描结束后处死动物，取肿瘤外周及中心区域的组织进行免疫组化染色检测，得到肿瘤不同区域的微血管密度（MVD ）及血管内皮生长因子（VEGF）的表达情况，将DCE-MRI各参数与免疫组化结果进行相关分析。结果：对照组中肿瘤外周区域和中心区域的Ktrans值在治疗前分别为（32．58±3．10）和（28．50±3．54）min－1，治疗后分别为（37．66±2．78）和（34．20±3．39）min－1；实验组中肿瘤组织的外周区域和中心区域的Ktrans值在治疗前分别为（27．70±4．75）和（23．90±4．40）min－1，在治疗后分别为（22．20±4．29）和（18．30±4．23）min－1。实验组VX2骨肿瘤外周区域与中心区域的Ktrans值、MVD值及VEGF表达情况间的差异均有统计学意义（P＜0．05），Kep值的差异无统计学意义（P＞0．05）。实验组治疗后肿瘤外周和中心区域的VEGF表达、MVD值与Ktrans值间均呈正相关关系（r值分别为0．924、0．945、0．848和0．909，P＜0．01）；与Kep值间均无显著相关性（r值分别为0．022、0．162、0．219和0．042，P＞0．01）。结论：兔VX2骨肿瘤模型的血流灌注空间分布具有异质性；基于Reference模型的DCE-MRI定量参数Ktrans可以评价恩度对兔VX2骨肿瘤抗血管生成的疗效。
목적：탐토기우Reference-Region모형적DCE-MRI 평개은도대토VX2골종류항혈관생성료효적가행성。방법：장성공건립경골VX2종류모형（연조직종괴직경＞1．0 cm）적20지토자수궤분성대조조（n＝10）화실험조（n＝10），분별우급약전、련속급약14천후（대조조약물위생리염수；실험조약물위은도，약물농도위1．5 mg／8 mL）행DCE-MRI소묘，사용Referrence Region모형획득종류조직적대비제용적전이상량Ktrans화반류속솔상수Kep。우제14천소묘결속후처사동물，취종류외주급중심구역적조직진행면역조화염색검측，득도종류불동구역적미혈관밀도（MVD ）급혈관내피생장인자（VEGF）적표체정황，장DCE-MRI각삼수여면역조화결과진행상관분석。결과：대조조중종류외주구역화중심구역적Ktrans치재치료전분별위（32．58±3．10）화（28．50±3．54）min－1，치료후분별위（37．66±2．78）화（34．20±3．39）min－1；실험조중종류조직적외주구역화중심구역적Ktrans치재치료전분별위（27．70±4．75）화（23．90±4．40）min－1，재치료후분별위（22．20±4．29）화（18．30±4．23）min－1。실험조VX2골종류외주구역여중심구역적Ktrans치、MVD치급VEGF표체정황간적차이균유통계학의의（P＜0．05），Kep치적차이무통계학의의（P＞0．05）。실험조치료후종류외주화중심구역적VEGF표체、MVD치여Ktrans치간균정정상관관계（r치분별위0．924、0．945、0．848화0．909，P＜0．01）；여Kep치간균무현저상관성（r치분별위0．022、0．162、0．219화0．042，P＞0．01）。결론：토VX2골종류모형적혈류관주공간분포구유이질성；기우Reference모형적DCE-MRI정량삼수Ktrans가이평개은도대토VX2골종류항혈관생성적료효。
Objective:To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)based on the Reference-Region model for evaluating anti-tumor angiogenesis effect of endostar in rabbit VX2 bone tumor.Methods:20 rabbits with VX2 bone tumor (tumor size in soft tissue>1cm)were randomly divided into the control group (n= 10)and the experimental group (n= 10),and were accepted DCE-MRI examination before and 14 days after treatment (using saline in control group;using endostar with concentration of 1.5mg/8mL in experimental group).DCE-MRI parameters including microvascular permeability transfer constant (Ktrans )and microvascular permeability reflux con-stant (Kep )were acquired based on the Reference-Region model.All the rabbits were sacrificed after DCE-MRI scanning at the 14th day.MVD and VEGF expression were analyzed by immunohistochemical staining.Correlation analysis was per-formed between DCE-MRI parameters and immunohistochemistry results.Results:In the experimental group,the Ktrans , MVD and VEGF expression had statistical difference (P<0.05)between peripheral region and central region of tumors, but the Kep value had no statistical difference (P>0.05)between the two regions.Before treatment,the Ktrans value of pe-ripheral region and central region of rabbit VX2 bone tumors in the control group were (32.58±3.10)and (28.5± 3.54)min-1 respectively;and were (27.7±4.75)and (23.9±4.40)min-1 in the experimental group;after treatment,they were (37.66±2.78)and (34.2±3.39)min-1 in control group,and were (22.2±4.29)and (18.3±4.23)min-1 in the ex-perimental group,respectively.In the experimental group,the Ktrans values of the peripheral region and central region of rab-bit VX2 bone tumors were correlated with the MVD and VEGF expression (r= 0.924,0.945,0.848 and 0.909,respective-ly;P<0.01).The Kep values were not correlated with the MVD and the VEGF expression (r= 0.022,0.162,0.219 and 0.042,respectively;P>0.01).Conclusion:The spatial distribution of blood perfusion in rabbit VX2 bone tumors has hetero-geneity.The Ktrans value in DCE-MRI based on the Reference-Region model can be applied to estimate the anti-tumor angio-genesis effect of endostar.