^(68)Ga-citrate对软组织感染PET-CT显像基因表达分子机制与验证  

Molecular mechanisms and validation of gene expression in ^(68)Ga-citrate PET-CT imaging of soft tissue infections

作　　者：徐婷婷 江飞 傅文会 陈跃 XU Tingting;JIANG Fei;FU Wenhui;CHEN Yue(Department of Nuclear Medicine,The Affiliated Hospital,Southwest Medical University,Luzhou 646000,China;Nuclear Medi-cine and Molecular Imaging Key Laboratory of Sichuan Province,Luzhou 646000,China;Institute of Nuclear Medicine,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院核医学科,泸州646000 [2]核医学与分子影像四川省重点实验室,泸州646000 [3]西南医科大学核医学研究所,泸州646000

出　　处：《西南医科大学学报》2024年第1期68-74,共7页Journal of Southwest Medical University

基　　金：核医学与分子影像四川省重点实验室开放课题(HYX19006);西南医科大学附属医院博士科研启动基金资助项目(19027);泸州市科技计划项目(2019-JYJ-57);西南医科大学校级科研项目(2021ZKQN066)。

摘　　要：目的研究^(68)Ga-citrate对软组织感染正电子发射计算机断层(PET-CT)显像分子机制相关基因Tfrc、Trf、和Ttf对感染应答的基因表达变化,探讨小鼠多药及毒性外排转运子1(multidrug and toxin extrusion1,mMATE1)在小鼠软组织感染的^(68)Ga-citrate PET-CT显像中可能的作用。方法用金黄色葡萄球菌感染小鼠形成脓肿,取不同时间点的脓肿组织,用荧光定量PCR(real-time PCR)鉴定Tfrc、Trf、Ttf基因和mMATE1基因Slc47a1的相对表达量。用^(68)Ga标记柠檬酸(citrate),阻断实验使用PET-CT技术研究mMATE1转运子在小鼠软组织感染^(68)Ga-citrate显像中的相关性。结果real-time PCR显示转铁蛋白TF基因Trf和乳铁蛋白TLF基因Ttf在4 d时间点表达量最高,mMATE1转运子基因Slc47a1的表达类型与转铁蛋白受体TFRC基因Tfrc类似,在1 h左右达到峰值,随后逐渐降低,而Na+偶联的柠檬酸转运子NaCT的基因SLC13A5表达量在所有时间点未有明显变化。Trf、Ttf、Slc47a1和Tfrc基因表达最高值与0 h时间点的表达量相比均有显著差异(57.21±11.62和7.53±1.74,t=35.38;43.03±6.8和6.26±1.32,t=12.05;28.79±2.16和8.21±1.23,t=8.22;1091.36±30.76和290.84±10.62,t=52.08;P<0.01),且Slc47a1基因表达最高值显著高于SLC13A5基因同时间点的基因表达量(28.79±2.16和1.67±0.51,t=79.81,P<0.01)。PET-CT显示^(68)Ga-citrate或^(68)GaCl3尾静脉注射不同处理对小鼠左后腿相应部位^(68)Ga聚集有显著影响(F=13.77,P<0.01),其中炎症小鼠感染部位有明显^(68)Ga聚集(SUVmax=3.87±0.32),而对照未感染部位未见明显^(68)Ga聚集(SUVmax=0.31±0.13),差异有统计学意义(t检验,P<0.01),mMATE1阻断的感染小鼠感染部位对^(68)Ga的摄取明显减少(SUVmax=1.62±1.03),与未阻断感染小鼠比较差异有统计学意义(t检验,P<0.05)。结论从分子水平上证实Tfrc、Trf和Ttf在感染处高表达,多药及毒素外排转运子mMATE1可能参与金黄色葡萄球菌诱导小鼠软组织感染的^(68)Ga-citrateObjective To investigate the changes in the gene expression of Tfrc、Trf、and Ttf related to the molecular mechanism of ^(68)Ga-citrate PET-CT imaging of soft tissue infections and explore the possible role of mMATE1 transporter in the ^(68)Ga-citrate PET-CT imaging of soft tissue infections in mice.Methods Mice were infected with Staphylococcus aureus to develop abscesses,and the rela-tive expression levels of Tfrc、Trf、Ttf and Slc47a1 genes were determined by real-time PCR at different time points.^(68)Ga-citrate was used for PET-CT imaging,and the blocking experiment was performed to investigate the correlation between mMATE1 transporter and ^(68)Ga-citrate PET-CT imaging of mouse infections.Results Real-time PCR demonstrated that the expression of genes for transferrin Trf and lactoferrin Ttf peaked at the time point of 4 days,and the expression pattern of transferrin receptor TFRC gene Tfrc was similar with that of Slc47a1,peaking at 1h time point and gradually decreasing with time.However,the gene expression of Na+coupled citrate transporter NaCT almost kept unchanged at all time points.There were significant differences between the peak value of gene expression for genes Trf、Ttf、Slc47a1 and Tfrc and those at 0 time points(57.21±11.62 and 7.53±1.74,t=35.38;43.03±6.8 and 6.26±1.32,t=12.05;28.79±2.16和8.21±1.23,t=8.22;1091.36±30.76 and 290.84±10.62,t=52.08;P<0.01).The highest value of Slc47a1 gene expression was significantly higher than that of SLC13A5 at the same time point(28.79±2.16 and 1.67±0.51,t=79.81,P<0.01).PET-CT displayed that different treatments had significant influence on the ^(68)Ga localization at the infected left hind legs af-ter ^(68)Ga-citrate or ^(68)GaCl3 injection intravenously(F=13.77,P<0.01).^(68)Ga-citrate apparently localized at infected sites(SUVmax=3.87±0.32)while the imaging agent rarely localized at sterile sits(SUVmax=0.31±0.13)and there was a significant difference be-tween both(t test,P<0.01).For the case of mMATE1 blocked,the localization of imaging ag

关 键 词：基因表达 ^(68)Ga-citrate感染 正电子发射计算机断层显像 多药及毒性化合物外排转运体1 

分 类 号：R817.1[医药卫生—影像医学与核医学]