Liu Huan, Davis Jacques R J, Wu Zhi-Lin, Faez Abdelgawad Amro
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Anesthesiology, ICU and Pain Management, Benha University Hospital, Faculty of Medicine, Benha University, Benha, Egypt.
Biomed Res Int. 2017;2017:6352159. doi: 10.1155/2017/6352159. Epub 2017 Feb 14.
. Neuroinflammation which presents as a possible mechanism of delirium is associated with MCP-1, an important proinflammatory factor which is expressed on astrocytes. It is known that dexmedetomidine (DEX) possesses potent anti-inflammatory properties. This study aimed to investigate the potential effects of DEX on the production of MCP-1 in lipopolysaccharide-stimulated astrocytes. . Astrocytes were treated with LPS (10 ng/ml, 50 ng/ml, 100 ng/ml, and 1000 ng/ml), DEX (500 ng/mL), LPS (100 ng/ml), and DEX (10, 100, and 500 ng/mL) for a duration of three hours; expression levels of MCP-1 were measured by real-time PCR. The double immunofluorescence staining protocol was utilized to determine the expression of 2-adrenoceptors (2AR) and glial fibrillary acidic protein (GFAP) on astrocytes. . Expressions of MCP-1 mRNA in astrocytes were induced dose-dependently by LPS. Administration of DEX significantly inhibited the expression of MCP-1 mRNA ( < 0.001). Double immunofluorescence assay showed that 2AR colocalize with GFAP, which indicates the expression of 2-adrenoceptors in astrocytes. . DEX is a potent suppressor of MCP-1 in astrocytes induced with lipopolysaccharide through A-adrenergic receptors, which potentially explains its beneficial effects in the treatment of delirium by attenuating neuroinflammation.
作为谵妄可能机制的神经炎症与单核细胞趋化蛋白-1(MCP-1)相关,MCP-1是一种在星形胶质细胞上表达的重要促炎因子。已知右美托咪定(DEX)具有强大的抗炎特性。本研究旨在探讨DEX对脂多糖刺激的星形胶质细胞中MCP-1产生的潜在影响。 将星形胶质细胞分别用脂多糖(10 ng/ml、50 ng/ml、100 ng/ml和1000 ng/ml)、DEX(500 ng/mL)、脂多糖(100 ng/ml)和DEX(10、100和500 ng/mL)处理三小时;通过实时聚合酶链反应测量MCP-1的表达水平。采用双重免疫荧光染色法测定星形胶质细胞上β2-肾上腺素能受体(β2AR)和胶质纤维酸性蛋白(GFAP)的表达。 脂多糖以剂量依赖方式诱导星形胶质细胞中MCP-1 mRNA的表达。给予DEX可显著抑制MCP-1 mRNA的表达(P<0.001)。双重免疫荧光分析显示β2AR与GFAP共定位,这表明星形胶质细胞中存在β2-肾上腺素能受体的表达。 DEX是脂多糖诱导的星形胶质细胞中MCP-1的有效抑制剂,其通过β-肾上腺素能受体发挥作用,这可能解释了其通过减轻神经炎症在谵妄治疗中的有益作用。