Excess salt intake promotes M1 microglia polarization via a p38/MAPK/AR-dependent pathway after cerebral ischemia in mice
Excess salt intake promotes M1 microglia polarization via a p38/MAPK/AR-dependent pathway after cerebral ischemia in mice
复制标题
小鼠脑缺血后过量盐摄入通过 p38/MAPK/AR 依赖性途径促进 M1 小胶质细胞极化
DOI：
10.1016/j.intimp.2019.106176
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发表时间：
2020
影响因子：
5.6
通讯作者：
Wang Guangyou
中科院分区：
文献类型：
--
作者：
Zhang Tongshuai;Wang D;an;Li Xuan;Jiang Yixiang;Wang Chao;Zhang Yao;Kong Qingfei;Tian Chao;Dai Yongfeng;Zhao Wei;Jiang Mingyue;Chang Yanzhong;Wang Guangyou
高盐饮食(HSD)是许多疾病最重要的危险因素之一。HSD加重脑缺血损伤的机制之一与血压变化无关。HSD在脑缺血后炎症中的直接作用尚不清楚。在本研究中，在高盐饮食喂养21天后，通过手术诱导小鼠永久性局灶性缺血。分别于缺血12h、1d、3d和5d分析HSD对损伤体积、小胶质细胞极化、醛糖还原酶(AR)表达和炎症过程的影响。我们报道，在小鼠中，过量的食盐促进炎症，并增加经典的脂多糖(LPS)诱导的小胶质细胞/巨噬细胞(M1)的激活。这种作用依赖于HSD小鼠永久性大脑中动脉结扎(PMCAL)后激活的小胶质细胞中AR蛋白的表达。给予AR抑制剂依帕瑞司或p38中和抗体可阻断小胶质细胞的极化，减轻卒中损伤。结论：HSD通过上调AR蛋白的表达而促进促炎性M1小胶质细胞的极化，从而加重缺血性卒中的发展。
A high salt diet (HSD) is among the most important risk factors for many diseases. One mechanism by which HSD aggravates cerebral ischemic injury is independent of blood pressure changes. The direct role of HSD in inflammation after cerebral ischemia is unclear. In this research, after twenty-one days of being fed a high salt diet, permanent focal ischemia was induced in mice via operation. At 12 h and 1, 3 and 5 days postischemia, the effects of HSD on the lesion volume, microglia polarization, aldose reductase (AR) expression, and inflammatory processes were analyzed. We report that in mice, surplus dietary salt promotes inflammation and increases the activation of classical lipopolysaccharide (LPS)-induced microglia/macrophages (M1). This effect depends on the expression of the AR protein in activated microglia after permanent middle cerebral artery ligation (pMCAL) in HSD mice. The administration of either the AR inhibitor Epalrestat or a p38-neutralizing antibody blocked the polarization of microglia and alleviated stroke injury.In conclusion, HSD promotes polarization in pro-inflammatory M1 microglia by upregulating the expression of the AR protein via p38/MAPK, thereby exacerbating the development of ischemia stroke.