Dynamic change of MMP-9 in diabetic stroke visualized by optical imaging and treated with CD28 superagonist
Dynamic change of MMP-9 in diabetic stroke visualized by optical imaging and treated with CD28 superagonist
复制标题
CD28超激动剂治疗糖尿病卒中中MMP-9的动态变化光学成像可视化
DOI：
10.1039/d0bm02014a
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发表时间：
2021-04-07
影响因子：
6.6
通讯作者：
Ju, Shenghong
中科院分区：
文献类型：
--
作者：
Cai, Yu;Leng, Shou;Ju, Shenghong
2型糖尿病与卒中风险增加和卒中后不良结局有关。基质金属蛋白酶-9(MMP9)是糖尿病缺血性卒中预后不良的潜在因素。由于缺乏非侵入性成像技术，对糖尿病卒中的研究受到限制。在本研究中，我们报道了一种快速、超灵敏的可激活基质金属蛋白酶的光学成像探针(MMPP12)，以实现对糖尿病卒中中基质金属蛋白酶9动态表达的无创性和实时可视化。此外，通过使用该探针，我们旨在检测CD28 SA对糖尿病卒中的治疗效果。分别于缺血后第1、3、7天注射基质金属蛋白酶-P12探针，对野生型和链脲佐菌素糖尿病小鼠进行连续近红外荧光成像。分别于卒中后第1、3、7天观察CD28-SA治疗后基质金属蛋白酶-9表达的动态变化，并用免疫组织化学染色和免疫印迹法证实。NIRF成像显示糖尿病卒中小鼠表现出较高水平的MMP9的趋势。在卒中后第7天，CD28SA治疗显著下调了基质金属蛋白酶-9的表达。CD28 SA治疗的糖尿病卒中小鼠的血糖也有下降的趋势。综上所述，我们的研究结果表明，利用光学成像技术，可以成功地检测到糖尿病卒中患者脑组织中基质金属蛋白酶-9的动态变化。CD28SA治疗可降低基质金属蛋白酶-9的表达，有望成为治疗糖尿病卒中的一种新的治疗策略。
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.