摘要
目的构建载转化生长因子-β1(transforming growth factor beta-1,TGF-β1)的超小超顺磁性氧化铁(ultrasmall supperparamagnetic iron oxide,USPIO)靶向探针(USPIO-anti-TGF-β1),探究其表征及磁共振成像(magnetic resonance imaging,MRI)靶向检测大鼠心肌纤维化(myocardial fibrosis,MF)模型中TGF-β1表达的可行性。材料与方法选择40只雄性SD大鼠,其中30只采用异丙肾上腺素(isoprenaline,ISO)皮下注射法建立MF模型,另外10只作为健康对照组。通过超声评估大鼠模型建立情况。将造模成功的30只大鼠随机分为实验组、单纯对照组及空白对照组,每组10只;构建USPIO-anti-TGF-β1靶向探针,通过尾静脉注入实验组大鼠体内,单纯对照组及空白对照组分别注入相同剂量的USPIO和生理盐水,并于注射12 h后行T2序列扫描。扫描完成后取大鼠心肌标本行病理学分析。采用独立样本t检验对给药前后的MRI信号强度变化进行分析。结果MRI示实验组给药前心肌信号尚均匀,给药12 h后心内膜下心肌可见信号减低区,二者相对信号强度具有明显差异(0.72±0.12 vs.0.62±0.10,P<0.01);单纯对照组与空白对照组给药前后心肌信号未见明显减低(0.73±0.12 vs.0.71±0.12,P=0.81;0.70±0.13 vs.0.74±0.13,P=0.52)。普鲁士蓝染色显示实验组MF区域与给药后MRI所示信号减低区相符合,免疫组化可见MF区域TGF-β1的阳性表达,普鲁士蓝染色显示心肌细胞中有大量铁颗粒的沉积,证实USPIO-anti-TGF-β1靶向探针的存在。结论通过USPIO-anti-TGF-β1靶向探针进行MRI在体检测MF大鼠模型中TGF-β1的表达可行,为临床监测TGF-β1的表达及抗MF治疗方案的选择和疗效评估提供了实验依据。
Objective:To explore the feasibility of targeted magnetic resonance imaging(MRI)to detect transforming growth factor beta-1(TGF-β1)expression by constructing superparamagnetic iron oxide(USPIO)nanoparticles that carry transforming growth factor-β1 antibody(TGF-β1).Materials and Methods:Forty male SD rats were selected,of which 30 were modeled by isoprenaline subcutaneous injection,while the other 10 were used as healthy controls.Myocardial fibrosis modeling was evaluated by ultrasound.The 30 successfully modeled rats were randomly divided into the experimental group,simple control group,and blank control group.A TGF-β1 targeting probe(USPIO-anti-TGF-β1)was constructed and injected into experimental rats through the tail vein.The simple control and blank control groups were injected with the same dose of simple USPIO and normal saline.T2 weighted imaging was performed after 12 hours of injection to observe the change in myocardial signal intensity in the three groups.After MRI was completed,rat myocardium was taken as a specimen for pathological analysis.Independent-samples t test was used to analyze the changes of MRI signals before and after injection.Results:Stable USPIO-anti-TGF-β1 probes were successfully prepared.MRI showed that the myocardial signal of rats in the experimental group remained uniform before administration.No significant low signal areas were observed.After 12 hours of administration,the subendocardial myocardium could be seen in the area of signal reduction.There was a significant difference in the relative signal strength of the two groups(0.72±0.12 vs.0.62±0.10,P<0.01);There was no significant decrease in myocardial signal between the simple control group and the blank control group before and after administration(0.73±0.12 vs.0.71±0.12,P=0.81;0.70±0.13 vs.0.74±0.13,P=0.52).Masson staining showed that the area of myocardial fibrosis in the experimental group was consistent with the area of signal reduction shown by the MRI after administration.Immunohistochemistry showed positi
作者
宋梦星
夏敏
杨雅雯
马占龙
SONG Mengxing;XIA Min;YANG Yawen;MA Zhanlong(Department of Radiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
出处
《磁共振成像》
CAS
CSCD
北大核心
2024年第4期120-125,132,共7页
Chinese Journal of Magnetic Resonance Imaging
基金
国家自然科学基金项目(编号:81971669)。
关键词
转化生长因子-Β1
超小超顺磁性氧化铁纳米颗粒
大鼠心肌纤维化模型
磁共振成像
transforming growth factor beta-1
ultrasmall supperparamagnetic iron oxide
targeting probe model of myocardial fibrosis in rat
magnetic resonance imaging
