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Dynamic change of MMP-9 in diabetic stroke visualized by optical imaging and treated with CD28 superagonist

机译:通过光学成像可视化MMP-9在糖尿病行程中的动态变化,并用CD28超方处理

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摘要

Type 2 diabetes mellitus is associated with an increased risk for stroke and unfavorable outcomes following stroke. Matrix metalloproteinase-9 (MMP-9) is a potential contributor to the poor prognosis of diabetic ischemic stroke. Investigations on diabetic stroke are limited by the lack of non-invasive imaging techniques. In this study, we report a fast and ultra-sensitive MMP-activatable optical imaging probe (MMP-P12) to achieve non-invasive and real-time visualization of the dynamic expression of MMP-9 in diabetic stroke. Moreover, by using this probe, we aim to detect the therapeutic efficacy of CD28 SA in diabetic stroke. Serial near-infrared fluorescence (NIRF) imaging was performed on wild-type and STZ-induced diabetic mice after MMP-P12 probe injection on days 1, 3, and 7 post ischemic stroke. The dynamic change in MMP-9 expression after CD28 SA treatment was also imaged on days 1, 3, and 7 post stroke and confirmed by immunohistochemistry staining and western blotting. NIRF imaging showed that diabetic stroke mice presented a trend of higher levels of MMP-9. CD28 SA treatment significantly downregulated the expression of MMP-9 on day 7 post stroke. Glucose also had a downward trend in CD28 SA treated diabetic stroke mice. In conclusion, our data suggest that MMP-P12 probe successfully detect the dynamic change of MMP-9 in diabetic stroke by utilizing optical imaging. CD28 SA treatment decreased the expression of MMP-9 and could be a promising therapeutic strategy for the treatment of diabetic stroke.
机译:2型糖尿病与中风后中风和不利结果的风险增加。基质金属蛋白酶-9(MMP-9)是患有糖尿病缺血性卒中不良的潜在因素。对糖尿病中风的研究受到缺乏非侵入性成像技术的限制。在这项研究中,我们报告了快速和超敏感的MMP活性光学成像探针(MMP-P12),以实现糖尿病行程中MMP-9的动态表达的非侵入性和实时可视化。此外,通过使用该探针,我们的目的是检测CD28SA在糖尿病中风中的治疗效果。在MMP-P12探针注射术后1,3和7个后缺血性卒中后,在野生型和STZ诱导的糖尿病小鼠上进行连续近红外荧光(NIRF)成像。 CD28 SA处理后MMP-9表达的动态变化也在第1,3天和7天后脑卒中成像,并通过免疫组织化学染色和蛋白质印迹证实。 NIRF成像表明,糖尿病卒中小鼠呈现了更高水平的MMP-9的趋势。 CD28 SA治疗显着下调了第7天后卒中MMP-9的表达。葡萄糖还具有CD28 SA治疗糖尿病卒中小鼠的下降趋势。总之,我们的数据表明MMP-P12探针通过利用光学成像,MMP-P12探针在糖尿病行程中成功地检测MMP-9的动态变化。 CD28 SA治疗降低了MMP-9的表达,并且可能是治疗糖尿病中风的有希望的治疗策略。

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  • 来源
    《Biomaterials Science》 |2021年第7期|共9页
  • 作者单位

    Southeast Univ Zhongda Hosp Dept Radiol Jiangsu Key Lab Mol &

    Funct Imaging Med Sch Nanjing 210009 Peoples R China;

    Southeast Univ Zhongda Hosp Dept Radiol Jiangsu Key Lab Mol &

    Funct Imaging Med Sch Nanjing 210009 Peoples R China;

    Southeast Univ Zhongda Hosp Dept Radiol Jiangsu Key Lab Mol &

    Funct Imaging Med Sch Nanjing 210009 Peoples R China;

    Southeast Univ Zhongda Hosp Dept Radiol Jiangsu Key Lab Mol &

    Funct Imaging Med Sch Nanjing 210009 Peoples R China;

    Southeast Univ Zhongda Hosp Dept Radiol Jiangsu Key Lab Mol &

    Funct Imaging Med Sch Nanjing 210009 Peoples R China;

    Southeast Univ Zhongda Hosp Dept Radiol Jiangsu Key Lab Mol &

    Funct Imaging Med Sch Nanjing 210009 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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