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缺血性中风小鼠中枢神经系统MHC-I分子的无创监测

Non-Invasive Monitoring of CNS MHC-I Molecules in Ischemic Stroke Mice.

作者信息

Xia Jing, Zhang Ying, Zhao Huanhuan, Wang Jie, Gao Xueren, Chen Jinpeng, Fu Bo, Shen Yuqing, Miao Fengqin, Zhang Jianqiong, Teng Gaojun

机构信息

Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.

Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

出版信息

Theranostics. 2017 Jul 8;7(11):2837-2848. doi: 10.7150/thno.18968. eCollection 2017.

Abstract

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. The expression of major histocompatibility complex class I (MHC-I) molecules in the central nervous system, which are silenced under normal physiological conditions, have been reported to be induced by injury stimulation. The purpose of this study was to determine whether MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke and to assess whether a high-affinity peptide specific for MHC-I molecules could be applied in the near-infrared imaging of cerebral ischemic mice. Quantitative real-time PCR and Western blotting were used to detect the expression of MHC-I molecules in two mouse models of cerebral ischemic stroke and an model of ischemia. The NetMHC 4.0 server was used to screen a high-affinity peptide specific for mouse MHC-I molecules. The Rosetta program was used to identify the specificity and affinity of the screened peptide (histocompatibility-2 binding peptide, H2BP). The results demonstrated that MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke. Cy5.5-H2BP molecular probes could be applied in the near-infrared imaging of cerebral ischemic mice. Research on the expression of MHC-I molecules in the acute phase after ischemia and MHC-I-targeted imaging may not only be helpful for understanding the mechanism of ischemic and hypoxic brain injury and repair but also has potential application value in the imaging of ischemic stroke.

摘要

缺血性中风是全球发病和死亡的主要原因之一。据报道,正常生理条件下沉默的中枢神经系统中主要组织相容性复合体I类(MHC-I)分子的表达可由损伤刺激诱导。本研究的目的是确定MHC-I分子是否可作为缺血性中风急性期的分子靶点,并评估针对MHC-I分子的高亲和力肽是否可应用于脑缺血小鼠的近红外成像。采用定量实时聚合酶链反应和蛋白质免疫印迹法检测两种脑缺血性中风小鼠模型和一种缺血模型中MHC-I分子的表达。利用NetMHC 4.0服务器筛选针对小鼠MHC-I分子的高亲和力肽。使用Rosetta程序鉴定筛选出的肽(组织相容性-2结合肽,H2BP)的特异性和亲和力。结果表明,MHC-I分子可作为缺血性中风急性期的分子靶点。Cy5.5-H2BP分子探针可应用于脑缺血小鼠的近红外成像。对缺血后急性期MHC-I分子表达及MHC-I靶向成像的研究,不仅有助于理解缺血缺氧性脑损伤及修复机制,而且在缺血性中风成像方面具有潜在的应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f3/5562219/69d9a90527da/thnov07p2837g001.jpg

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