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用于评估转基因小鼠中宿主与生物材料相互作用的无创性核因子-κB生物发光成像

Noninvasive nuclear factor-kappaB bioluminescence imaging for the assessment of host-biomaterial interaction in transgenic mice.

作者信息

Ho Tin-Yun, Chen Yueh-Sheng, Hsiang Chien-Yun

机构信息

Molecular Biology Laboratory, Graduate Institute of Chinese Medical Science, China Medical University, Taichung 40402, Taiwan.

出版信息

Biomaterials. 2007 Oct;28(30):4370-7. doi: 10.1016/j.biomaterials.2007.07.005. Epub 2007 Jul 23.

Abstract

The inflammatory response is a key component in the biocompatibility of biomaterials. Among the factors that control the development of inflammation is a critical molecule nuclear factor-kappaB (NF-kappaB). Therefore, the aim of this study was to assess the feasibility of noninvasive whole-body real-time imaging for the evaluation of host-biomaterial interaction in the NF-kappaB transgenic mice. Transgenic mice, carrying the luciferase gene under the control of NF-kappaB, were constructed. In vivo bioluminescence imaging showed that the constitutive and induced NF-kappaB activities of transgenic mice were detected in most of the lymphoid tissues, demonstrating that NF-kappaB-driven luminescence reflected the inflammatory response in vivo. By the implantation of genipin-cross-linked gelatin conduit (GGC) and bacterial endotoxin-immersed GGC in the dorsal region, we detected a strong and specific luminescent signal from the tissue around the bacterial endotoxin-immersed GGC implant. Histological and immunohistochemical analysis also demonstrated that inflammation, characterized by the infiltration of immune cells, the accumulation of fluid, and the activation of NF-kappaB, was evoked around the same region. The correlation between the bioluminescence imaging and histological changes indicated that noninvasive imaging technique could be used to monitor the real-time inflammation in the implanted mice.

摘要

炎症反应是生物材料生物相容性的关键组成部分。在控制炎症发展的因素中,关键分子是核因子-κB(NF-κB)。因此,本研究的目的是评估无创全身实时成像在评估NF-κB转基因小鼠宿主-生物材料相互作用中的可行性。构建了在NF-κB控制下携带荧光素酶基因的转基因小鼠。体内生物发光成像显示,在大多数淋巴组织中检测到转基因小鼠的组成型和诱导型NF-κB活性,表明NF-κB驱动的发光反映了体内的炎症反应。通过在背部区域植入京尼平交联明胶导管(GGC)和细菌内毒素浸泡的GGC,我们在细菌内毒素浸泡的GGC植入物周围的组织中检测到强烈而特异的发光信号。组织学和免疫组织化学分析也表明,在同一区域周围引发了以免疫细胞浸润、液体蓄积和NF-κB激活为特征的炎症。生物发光成像与组织学变化之间的相关性表明,无创成像技术可用于监测植入小鼠的实时炎症。

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