负荷试验CT灌注成像结合HIF1α、MMP2及VEGF评价大鼠C6胶质瘤侵袭力  

Stress CT perfusion imaging combined with HIF1α,MMP2 and VEGF in evaluating the invasiveness of rat with C6 glioma

作　　者：李竹君 陆娜 于洋 刘颖 LI Zhu-jun;LU Na;YU Yang;LIU Ying(Department of Pathology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;Department of Radiology,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学基础医学院病理学系,上海200032 [2]复旦大学附属华山医院放射科,上海200040

出　　处：《复旦学报（医学版）》2022年第3期326-331,共6页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金(81701686)。

摘　　要：目的探寻负荷试验CT灌注成像中可以无创评估神经胶质瘤侵袭性的影像学生物标志物。方法取20只雄性大鼠随机分为4组,其中3组分别在原位种植C6胶质瘤10、14、18天后行CT灌注成像,1组注射生理盐水作为对照。在乙酰唑胺负荷前后进行CT灌注,收集并分析各项灌注生物标志物。再取各组鼠脑开展病理学检验,进行缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF1α)、基质金属蛋白酶2(matrix metalloproteinase 2,MMP2)及血管内皮生长因子(vascular endothelial growth factor,VEGF)免疫组织化学染色。结果乙酰唑胺负荷后脑血流量(cerebral blood flow,CBF)、脑血容量(cerebral blood volume,CBV)和表面通透性(surface-permeability,PS)明显高于负荷前;随肿瘤种植天数的增加,CBF、CBV和PS百分比变化率随之降低,尤其是18天组与对照组之间比较:对照组分别为119.5%±21.2%、125.6%±9.0%、816.2%±116.4%,而18天组分别为54.6%±2.0%、24.5%±4.3%、4.5%±0.8%;HIF1α、MMP2及VEGF阳性率和CBF、CBV、PS百分比变化率之间呈显著负相关(P均<0.01)。结论负荷试验CT灌注成像的影像学生物标志物CBF、CBV和PS百分变化率可以无创评价大鼠C6胶质瘤的侵袭性。Objective To look for imaging biomarkers that can evaluate the invasiveness of gliomas in non-invasive way in stress CT perfusion imaging.Methods Twenty male Sprague-Dawley rats were randomized into four groups:five rats with orthotopically implanted C6 gliomas at 10-day old,five with gliomas at 14-day old,five with gliomas at 18-day old and five with orthotopically injected normal saline served as controls.CT perfusion was performed pre-and post-acetazolamide challenge.Then changes of perfusion parameters were collected and analyzed.The mouse brains of each group were taken for pathological examination,and immunohistochemical staining for hypoxia-inducible factor-1α(HIF1α),matrix metalloproteinase 2(MMP2)and vascular endothelial growth factor(VEGF)was performed.Results The differences in cerebral blood flow(CBF),cerebral blood volume(CBV)and surfacepermeability(PS)between the pre-and post-challenge were statistically significant,with the values were higher post acetazolamide than pre-challenge.CBF,CBV and PS percentage changes decreased markedly as the number of days of tumor implantation increased,especially between 18-day group and control:The percentage change rates of CBF,CBV,and PS in the control group were 119.5%±21.2%,125.6%±9.0%and 816.2%±116.4%,while the percentage change rates of CBF,CBV,and PS in 18-day group were 54.6%±2.0%,24.5%±4.3%and 4.5%±0.8%,respectively.Negative correlations were detected between HIF1α,MMP2,VEGF and CBF pre-challenge,CBV pre-challenge,PS pre-challenge.Negative correlations were found between HIF1α,MMP2,VEGF positive rate and CBF,CBV,PS percentage changes(All P values less than 0.01).Conclusion Imaging biomarkers of CT perfusion with challenge can reflect the invasiveness of rat with C6 glioma tumor in non-invasive way.

关 键 词：胶质瘤 灌注成像 肿瘤侵袭性 大鼠 

分 类 号：R365[医药卫生—病理学]