郭琳,桑楠.不同季节大气可吸入颗粒物(PM10)诱导小鼠原代培养神经元炎性及其级联损伤效应[J].环境科学学报,2015,35(1):311-316
不同季节大气可吸入颗粒物(PM10)诱导小鼠原代培养神经元炎性及其级联损伤效应
- Season-dependent particulate matter (PM10) exposure induces inflammatory response and cascade injury in mouse cortical neurons
- 基金项目：教育部高等学校博士学科点专项科研基金(No.20121401110003,20131401110005)
- 郭琳
- 山西大学环境与资源学院, 环境与健康研究中心, 环境科学研究所, 太原 030006
- 桑楠
- 山西大学环境与资源学院, 环境与健康研究中心, 环境科学研究所, 太原 030006
- 摘要：为了探讨不同季节可吸入颗粒物(PM10)对神经元的损伤效应,本研究通过建立小鼠大脑皮层原代神经元体外染毒模型,考察了不同季节PM10对炎性因子诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)和黏附分子(ICAM-1)表达水平的影响,并探讨了与之耦联的磷酸化Ca2+/钙调蛋白依赖性蛋白激酶Ⅱα(p-CaMKⅡα)、环磷腺苷效应元件结合蛋白(p-CREB)及即早基因(c-jun、c-fos)的表达情况.结果表明,PM10暴露刺激神经元炎性细胞因子释放增加,显著上调p-CaMKⅡα和p-CREB的水平,并刺激即早基因的高表达,且以冬季PM10的效应最为明显.由此提示,PM10暴露可能通过炎症反应机制激活Ca2+-CaMK-CREB通路,进而刺激即早基因表达引发神经毒性作用,而冬季PM10中多环芳烃类物质负荷可能是造成效应季节性差异的主要原因.
- Abstract：To study the association between season-dependent PM10 exposure and neurotoxicity, we set up exposure model of mouse primary cultured cortical neurons, and determined the effects of season-dependent PM10 on the expression of inflammatory marker inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and intercellular cell adhesion molecule-1(ICAM-1), and following cascade phosphorylated Calmodulin-dependent protein kinase II α (p-CaMKⅡα), phosphorylated cAMP-responsive element binding protein (p-CREB) and immediate early genes (c-jun and c-fos). Our results indicated that PM10 exposure significantly stimulated inflammatory cytokine release, up-regulated the levels of p-CaMKⅡα and p-CREB, and elevated the expression of c-jun and c-fos; the actions were season-dependent and the most obvious effect occurred after winter-originated sample treatment. It implies that PM10 exposure might stimulate the Ca2+-CaMK-CREB signal transduction pathway via inflammatory mechanism, then activated the immediate early genes, and finally caused neurotoxicity. Also, overloaded polycyclic aromatic hydrocarbons in winter sample might contribute to the explanation for the seasonal differences.
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