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应用纵向非侵入性双工分子光学成像评估鼠胶原诱导性关节炎。

Assessment of murine collagen-induced arthritis by longitudinal non-invasive duplexed molecular optical imaging.

机构信息

Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, MD Biosciences.

MD Biosciences.

出版信息

Rheumatology (Oxford). 2016 Mar;55(3):564-72. doi: 10.1093/rheumatology/kev361. Epub 2015 Oct 16.

Abstract

OBJECTIVE

In the present study we evaluated the use of four commercially available fluorescent probes to monitor disease activity in murine CIA and its suppression during glucocorticoid therapy.

METHODS

Arthritis was induced in male DBA/1 mice by immunization with type II collagen in Complete Freund's Adjuvant, followed by a boost of collagen in PBS. Four fluorescent probes from PerkinElmer in combination [ProSense 750 fluorescent activatable sensor technology (FAST) with Neutrophil Elastase 680 FAST and MMPSense 750 FAST with CatK 680 FAST] were used to monitor disease development from day 5 through to day 40 post-immunization. Fluorescence generated in vivo by the probes was correlated with clinical and histological score and paw measurements.

RESULTS

The fluorescence intensity emitted by each probe was shown to correlate with the conventional measurements of disease. The highest degree of correlation was observed with ProSense 750 FAST in combination with Neutrophil Elastase 680 FAST; these probes were then used to successfully assess CIA suppression during dexamethasone treatment.

CONCLUSION

We have demonstrated that longitudinal non-invasive duplexed optical fluorescence imaging provides a simple assessment of arthritic disease activity within the joints of mice following the induction of CIA and may represent a powerful tool to monitor the efficacy of drug treatments in preclinical studies.

摘要

目的

在本研究中,我们评估了四种市售荧光探针在监测 CIA 小鼠疾病活性及其在糖皮质激素治疗中的抑制作用。

方法

通过在完全弗氏佐剂中免疫 II 型胶原,随后在 PBS 中加强胶原,在雄性 DBA/1 小鼠中诱导关节炎。我们使用了来自 PerkinElmer 的四种荧光探针(ProSense 750 荧光可激活传感器技术(FAST)与中性粒细胞弹性蛋白酶 680 FAST 和 MMPSense 750 FAST 与 CatK 680 FAST),从免疫后第 5 天到第 40 天监测疾病的发展。体内探针产生的荧光与临床和组织学评分以及爪子测量值相关。

结果

每种探针发出的荧光强度均与疾病的常规测量相关。ProSense 750 FAST 与中性粒细胞弹性蛋白酶 680 FAST 的组合观察到相关性最高;然后使用这些探针成功评估了地塞米松治疗期间 CIA 的抑制作用。

结论

我们已经证明,纵向非侵入性双光子光学荧光成像提供了 CIA 诱导后小鼠关节内关节炎疾病活性的简单评估方法,可能代表了监测临床前研究中药物治疗效果的有力工具。

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