MR Imaging of activated hepatic stellate cells in liver injured by CCl4 of rats with integrin-targeted ultrasmall superparamagnetic iron oxide
MR Imaging of activated hepatic stellate cells in liver injured by CCl4 of rats with integrin-targeted ultrasmall superparamagnetic iron oxide
复制标题
整合素靶向超小超顺磁性氧化铁对四氯化碳损伤大鼠肝脏中活化肝星状细胞的磁共振成像
DOI：
10.1007/s00330-010-1988-z
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发表时间：
2011-05-01
影响因子：
5.9
通讯作者：
Wang, Deng-Bin
中科院分区：
文献类型：
--
作者：
Wang, Qing-Bing;Han, Yu;Wang, Deng-Bin
目的：探讨超小超顺磁性氧化铁（USPIO）环（Arg-Gly-Asp-Try-Cys）肽（c（RGDyC）-USPIO）靶向肝星状细胞（HSC）的可行性。在体外研究c（RGDyC）-USPIO对HSC的特异性。在体内，用c（RGDyC）-USPIO或USPIO处理正常和纤维化大鼠，并且在施用探针4小时后进行大鼠的磁共振成像（MRI）。结果：c（RGDyC）-USPIO的流体动力学尺寸为13 ± 3 nm。HSCs比普通的HSCs能更好地吸收特异性探针。c（RGDyC）-USPIO对纤维化大鼠T2弛豫时间的缩短作用明显大于USPIO（P < 0.05）。结论：c（RGDyC）-USPIO靶向α（v）β（3）整合素对肝纤维化中活化的HSCs进行体内细胞靶向成像是可行的。
Objective:To demonstrate the feasibility of the ultrasmall superparamagnetic iron oxide (USPIO) modified by cyclo (Arg-Gly-Asp-Try-Cys) peptide (c(RGDyC)-USPIO) for targeting hepatic stellate cells (HSCs).Materials and methods:A c(RGDyC)-USPIO probe was prepared by conjugating c(RGDyC) with USPIO through a thiol-maleinide interaction. The specificity of c(RGDyC)-USPIO for HSCs was investigated in vitro. In vivo, normal and fibrosis rats were treated with either c(RGDyC)-USPIO or USPIO, and magnetic resonance imaging (MRI) of the rats performed after administration of the probes for 4 h. The T2 relaxation times changes before and after probe injection were analyzed and the locations of probes in normal or injured mice were identified histologically.Results:The hydrodynamic size of c(RGDyC)-USPIO was 13 ± 3 nm. HSCs took up more specific probes than plain ones. The reduction of T2 relaxation times in fibrosis rat by c(RGDyC)-USPIO was much greater than that by USPIO (P < 0.05). Prussian blue staining and transmission electron microscopy of the injured rat liver treated with c(RGDyC) demonstrated that c(RGDyC)-USPIO were specifically engulfed by the activated HSCs.Conclusion:In vivo cellular targeted imaging of activated HSCs in liver fibrosis using c(RGDyC)-USPIO targeting α(v)β(3) integrins was feasible using a clinical 1.5-Tesla MR system.