EC-外泌体通过miR-126/ABCA1通路介导糖尿病脑卒中的神经再塑

Diabetes mellitus (DM) is a prominent risk factor for ischemic stroke.T2DM patients has a distinct clinical pattern and a poor prognosis compared to non-DM stroke. There is a compelling need to develop therapeutic approaches specifically designed to reduce neurological deficits after stroke in diabetic population. We found that T2DM mice exhibit significantly decreased serum, brain tissue and brain EC miR-126 expression, and specific conditional knockout of EC miR-126 mice have significantly worse functional outcome after stroke as well as decreased brain ATP-binding cassette transporter A1(ABCA1). Our preliminary studies suggest that mouse brain endothelial cell secreted exosomes (EC-Exo) contain high levels of miR-126 and that EC-Exo treatment of stroke in T2DM mice significantly increases ischemic brain miR-126 and ABCA1 expression.miR-126 is an angiogenic miRNA and ABCA1 plays an important role in promoting axonal/white matter (WM) remodeling as well as vascular remodeling after stroke. We propose that treatment of stroke with EC-Exo will enhance neurorestorative effects after stroke in T2DM mice and the miR-126/ABCA1 signaling pathway underpins therapeutic effect of EC-Exo. Our studies will provide fundamental insights into neurorestorative therapy on stroke in DM populations and a fresh approach for studies on stroke with comorbidities

糖尿病是缺血性脑卒中的一个重要危险因素。糖尿病脑卒中患者临床症状恶化、预后不良且复发率高。针对合并糖尿病的脑卒中患者的有效治疗是一个亟待解决的问题，我们前期研究发现：2型糖尿病会降低体内miR-126和ABCA1的基因表达水平，且神经功能损害严重。miR-126调节血管生长和成熟并促进白质的修复。小鼠脑内皮细胞分泌的外泌体（EC-Exo）中含有高水平的miR-126，并且miR-126可以上调ABCA1的表达。我们设想：应用EC-Exo治疗合并2型糖尿病的脑卒中小鼠，上调脑miR-126和ABCA1的表达，继而促进脑血管及脑白质重塑，从而改善卒中后神经功能恢复。本研究将为糖尿病脑卒中的神经功能恢复治疗研究奠定基础，并对合并其他疾病的脑卒中研究提供理论依据和借鉴。

糖尿病是缺血性脑卒中的一个重要危险因素。糖尿病脑卒中患者临床症状恶化、预后不良且复发率高。针对合并糖尿病的脑卒中患者的有效治疗是一个亟待解决的问题，我们前期研究发现：2型糖尿病会降低体内miR-126和ABCA1的基因表达水平，且神经功能损害严重。miR-126调节血管生长和成熟并促进白质的修复。小鼠脑内皮细胞分泌的外泌体（EC-Exo）中含有高水平的miR-126，并且miR-126可以上调ABCA1的表达。我们设想：应用EC-Exo治疗合并2型糖尿病的脑卒中小鼠，上调脑miR-126和ABCA1的表达，继而促进脑血管及脑白质重塑，从而改善卒中后神经功能恢复。本研究将为糖尿病脑卒中的神经功能恢复治疗研究奠定基础，并对合并其他疾病的脑卒中研究提供理论依据和借鉴。