An experimental study on magnetic resonance imaging tracking iron metabolism in rat brain based on transferrin receptor

ZHANG Yesen; LI Ning; SHANG Yuchun; HU Beiquan

doi:10.3969/j.issn.1674-3806.2024.10.11

Abstract：Objective To explore the application effect of magnetic resonance imaging(MRI)tracking iron metabolism in rat brain based on transferrin receptor(TfR),and to provide reference for clinical development of methods to monitor the therapeutic effect of Alzheimer's disease.Methods Twelve healthy adult Sprague-Dawley(SD)rats were selected and randomly divided into experimental group and control group,with 6 rats in each group.In the rats of the experimental group,TfR lentiviruses were injected into the striatum of the left cerebral hemisphere(TfR transfection group),and empty vector EGFP lentiviruses were injected into the striatum of the right cerebral hemisphere(EGFP transfection group).In the rats of the control group,the same volume of normal saline was injected into both sides of the striatum of the cerebral hemisphere(normal group).Two weeks later,transferrin(Tf)-conjugate of ultra-small super-paramagnetic iron oxide nanoparticles(USPIO)(Tf-USPIO)tracer was injected into the femoral vein of the rats at dose of 15 mg/kg,and MRI examination was performed for the rats before the injection and 1 day after the injection.After the MRI examination was completed,the rats were anesthetized with sodium pentobarbital and were sacrificed by using cervical dislocation method,and the brain striatum tissues of the rats were collected for immunofluorescence staining and Prussian blue staining.Real-time quantitative polymerase chain reaction(PCR)was used to detect the expression of TfR mRNA of the brain striatum tissues in rats.Results The results of real-time quantitative PCR showed that the expression level of TfR mRNA of the brain tissues in the TfR transfection group was significantly higher than that in the EGFP transfection group and the normal group(P＜0.05).The results of immunofluorescence staining and Prussian blue staining showed that TfR lentiviruses were successfully transfected into the brain tissues of the rats and the iron accumulation in the brain of Alzheimer's disease was successfully simulated.Before and after the injection of Tf-USPIO tracer,there were no significant changes in the MRI examination results of the rats in the control group,and obvious signal changes were observed in the left striatum of the rats in the experimental group and no obvious signal changes were observed in the right striatum of the rats in the experimental group.Conclusion Tf-USPIO tracer can specifically bind to TfR in brain tissues and can be displayed through MRI,providing a reference for the clinical development of methods to monitor the therapeutic effect of Alzheimer's disease.