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肌腱修复过程中血管生成的体内监测:大鼠髌腱模型中基于磁共振成像的新技术。

In vivo monitoring of angiogenesis during tendon repair: a novel MRI-based technique in a rat patellar tendon model.

作者信息

Stange Richard, Sahin Hacer, Wieskötter Britta, Persigehl Thorsten, Ring Janine, Bremer Christoph, Raschke Michael J, Vieth Volker

机构信息

Department of Trauma, Hand and Reconstructive Surgery, University Hospital Münster, Münster, Germany.

Department of Trauma, Hand and Reconstructive Surgery, Institute of Experimental Musculoskeletal Medicine (IEMM), University Hospital Münster, Waldeyerstr. 1, 48161, Münster, Germany.

出版信息

Knee Surg Sports Traumatol Arthrosc. 2015 Aug;23(8):2433-2439. doi: 10.1007/s00167-014-2897-5. Epub 2014 Feb 12.

DOI:10.1007/s00167-014-2897-5
PMID:24519623
Abstract

PURPOSE

Recent in vivo studies were able to show the impairing effect of neoangiogenesis in degenerative tendon diseases. Clinical in vivo monitoring of angiogenesis in injured tendons therefore seems to be crucial for an accurate therapeutic approach. The aim of this study was to develop a novel magnetic resonance imaging (MRI)-based technique for observing angiogenesis during tendon healing in vivo.

METHODS

Tendinopathy was induced by an in situ freezing model of rat patellar tendon and monitored after 7, 14, and 28 days. Animals were randomly divided into an imaging and immunohistochemical group. MRI with a 'blood pool' contrast agent was used to determine neoangiogenesis during tendon healing. MRI was compared to histochemical staining and quantification of blood vessels in injured and native tendons.

RESULTS

MRI data revealed a peak in changes in the transverse relaxation rate (ΔR 2*), which is proportional to relative blood volume, 7 days after surgery and decrease until day 28. Histological microvessel density and vascular endothelial growth factor synthesis were also most evident at day 7 and decreased over time.

CONCLUSIONS

The current results are demonstrating a time-dependent correlation between microvessel density and ΔR 2*. Thus, MRI-based evaluation of angiogenesis in the tendon might be a new promising technique for in vivo monitoring of angiogenesis and therapy response in the future.

摘要

目的

最近的体内研究表明新生血管生成在退行性肌腱疾病中具有损害作用。因此,对损伤肌腱中的血管生成进行临床体内监测对于准确的治疗方法似乎至关重要。本研究的目的是开发一种基于磁共振成像(MRI)的新技术,用于在体内观察肌腱愈合过程中的血管生成。

方法

通过大鼠髌腱原位冷冻模型诱导肌腱病,并在7天、14天和28天后进行监测。将动物随机分为成像组和免疫组织化学组。使用带有“血池”造影剂的MRI来确定肌腱愈合过程中的新生血管生成。将MRI结果与损伤肌腱和正常肌腱中的血管组织化学染色及血管定量结果进行比较。

结果

MRI数据显示,术后7天横向弛豫率(ΔR 2*)变化出现峰值,该值与相对血容量成正比,随后至28天逐渐下降。组织学微血管密度和血管内皮生长因子合成在第7天也最为明显,并随时间下降。

结论

目前的结果表明微血管密度与ΔR 2*之间存在时间依赖性相关性。因此,基于MRI评估肌腱中的血管生成可能是未来体内监测血管生成和治疗反应的一种新的有前景的技术。

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J Orthop Res. 2012 Dec;30(12):1952-7. doi: 10.1002/jor.22147. Epub 2012 May 21.
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Histologic stages of healing correlate with restoration of tensile strength in a model of experimental tendon repair.组织学愈合阶段与实验性肌腱修复模型中拉伸强度的恢复相关。
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