Experimental study on expression of TGF-β1 in fibrotic myocardium of rat by magnatic resonance targeted imaging
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 positive expression of TGF-β1 in the myocardial fibrosis region.Prussian blue staining showed the deposition of iron particles in cardiomyocytes,which confirmed the presence of the USPIO-anti-TGF-β1 probe.Conclusions:USPIO-anti-TGF-β1 probe can target magnetic resonance imaging of myocardial fibrosis,providing unprecedented ideas for the early diagnosis of myocardial fibrosis,providing experimental basis for monitoring of TGF-β1 expression and the selection and evaluation of anti fibrosis therapies.
transforming growth factor beta-1ultrasmall supperparamagnetic iron oxidetargeting probe model of myocardial fibrosis in ratmagnetic resonance imaging