Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China.
Department of Anesthesiology, Shenzhen SAMII Medical Center, Shenzhen, 518118, China.
Neurosci Bull. 2020 Sep;36(9):1035-1045. doi: 10.1007/s12264-020-00544-0. Epub 2020 Jul 18.
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.
缺血性脑卒中是全球范围内主要的致死病因之一。在脑卒中后阶段，心脏功能障碍很常见，被称为脑-心相互作用。糖尿病会使脑卒中后的预后恶化。脑卒中引起的全身炎症是导致后续并发症的主要因素，但糖尿病患者脑-心相互作用的机制尚未阐明。NLRP3（NLR 包含 pyrin 结构域 3）炎性小体是脑卒中后炎症的一个重要组成部分，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 2 型糖尿病小鼠模型的缺血性脑卒中引起的心脏功能障碍更为严重。同时，糖尿病性脑卒中后心脏心室中 M1 极化的巨噬细胞浸润和 NLRP3 炎性小体激活增加。重要的是，NLRP3 炎性小体抑制剂 CY-09 恢复了心脏功能，表明 M1 极化的巨噬细胞-NLRP3 炎性小体激活是糖尿病性脑卒中后脑-心相互作用的一种途径。
