Department of Neurobiology, Harbin Medical University, Harbin 150081, China.
Wu Lian De Memorial Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
Int Immunopharmacol. 2020 Apr;81:106176. doi: 10.1016/j.intimp.2019.106176. Epub 2020 Feb 7.
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.
高盐饮食（HSD）是许多疾病的最重要危险因素之一。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。在这项研究中，通过手术在喂食高盐饮食 21 天后诱导小鼠永久性局灶性脑缺血。在缺血后 12 小时和 1、3 和 5 天，分析 HSD 对病变体积、小胶质细胞极化、醛糖还原酶（AR）表达和炎症过程的影响。我们报告说，在小鼠中，过量的膳食盐促进炎症，并增加经典脂多糖（LPS）诱导的小胶质细胞/巨噬细胞（M1）的激活。这种作用取决于永久性大脑中动脉结扎（pMCAL）后 HSD 小鼠中激活的小胶质细胞中 AR 蛋白的表达。AR 抑制剂 Epalrestat 或 p38 中和抗体的给药阻断了小胶质细胞的极化，并减轻了中风损伤。总之，HSD 通过 p38/MAPK 上调 AR 蛋白的表达促进促炎 M1 小胶质细胞的极化，从而加重缺血性中风的发展。
