Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes
Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes
复制标题
糖尿病小鼠模型中缺血性中风后巨噬细胞-NLRP3炎症小体激活加剧心脏功能障碍
DOI：
10.1007/s12264-020-00544-0
复制
发表时间：
2020-07-18
影响因子：
5.6
通讯作者：
Zhang, Hong-Fei
中科院分区：
文献类型：
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作者：
Lin, Hong-Bin;Wei, Guan-Shan;Zhang, Hong-Fei
缺血性中风是世界范围内死亡的主要原因之一。在中风后阶段，心功能障碍是常见的，被称为脑-心相互作用。糖尿病是卒中后的预后因素。脑卒中引起的全身炎症反应是糖尿病并发症的主要原因，但糖尿病脑心相互作用的机制尚不清楚。NLRP 3（NLR pyrin domain-containing 3）炎性小体是脑卒中后炎症反应的重要组成部分，主要在M1极化的巨噬细胞中被激活。在这项研究中，我们发现缺血性中风引起的心功能障碍在2型糖尿病小鼠模型中更为严重。同时，M1极化的巨噬细胞浸润和NLRP 3炎性小体激活增加，在糖尿病中风后的心室。重要的是，NLRP 3炎性体抑制剂CY-09恢复了心脏功能，表明M1-极化巨噬细胞-NLRP 3炎性体激活是糖尿病卒中后脑-心相互作用的潜在途径。
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.