摘要
为了解低浓度二氧化硫(SO2)慢性暴露对神经系统炎症反应的影响,通过建立Wistar大鼠SO2动式吸入染毒模型,采用荧光免疫组织化学方法考察低浓度SO2(3.5和7 mg/m3)慢性暴露下大鼠大脑皮层胶质细胞的活化反应,通过实时荧光定量PCR方法考察炎性因子的基因转录水平,并通过蛋白免疫印迹Western blot方法初步考察对与神经功能相关的胞外信号调节激酶亚型1和2(Extracellularly regulated kinase 1/2,ERK1/2)及核转录因子环磷腺苷效应元件结合蛋白(c AMP response element-binding protein,CREB)信号途径的影响.结果显示,长期低浓度SO2暴露增加大脑皮层星形胶质细胞和小胶质细胞的活化反应,最高暴露组分别为对照组的2.07倍和2.12倍;诱导大鼠大脑皮层中促炎症因子TNFα和IL-1β的m RNA水平上调,最高暴露组分别为对照组的1.68和1.58倍;同时大鼠大脑皮层中诱导型环氧化酶(Cyclooxygenase-2,COX-2)和诱导型一氧化氮合酶(Inducible nitric oxide synthase,i NOS)的m RNA表达水平也明显增加,最高暴露组分别为对照组的1.59和1.45倍.此外,SO2暴露组大鼠大脑皮层中p-CREB和p-ERK1/2的蛋白表达减少,最高暴露组分别为对照组的0.73和0.74倍.本研究表明,慢性低浓度SO2暴露通过增加大鼠大脑皮层星形胶质细胞和小胶质细胞的活化反应,引起炎症因子TNFα、IL-1β、i NOS和COX-2 m RNA的高表达,而且会引起p-ERK1/2和p-CREB的蛋白表达水平下调,提示SO2暴露会通过炎症反应引起细胞信号传导和核转录的异常,导致神经功能损伤.
Sulfur dioxide （502）, a ubiquitous air pollutant, is now being considered to be involved in neurotoxicity and manybrain disorders via neuroinflammation. However, little is known about the impact of chronical SO2 inhalation on neuronal function. This paper aimed to investigate the impacts of chronical SO2 inhalation at low concentration on inflammation in rat cortex. Wistar rats were treated with different concentrations of SO2 （3.5 and 7 mg/m3） or filtered air 6 hours per day for 4 weeks, and the reactive astrocytes and microglia in rat cerebral cortex were determined by immunohistochemistry. The mRNA expression of inflammatory cytokines, tumor necrosis factor alpha （TNFa）, interleukin-1 beta （IL-lβ）, inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） in rat cerebral cortex were investigated by qRT-PCR. The expression of neuroplasticity related proteins, phosphorylated cyclic adenosine monophosphate response-element binding protein （p-CREB） and phosphorylated extracellular signal-regulated kinase subtype 1/2 （p-ERK1/2） were investigated by immunoblot. The results showed that SO2 inhalation significantly stimulated activation of astroglial cells and inflammatory cytokine releases in rat cerebral cortex. The mRNA expression of TNFa, IL-1β, COX-2 and iNOS in rats treated with higher concentration of SO2 were 1.68, 1.58, 1.59 and 1.45 folds, respectively, higher than that of the control. Moreover, the expression of p-ERK1/2 and p-CREB in rats exposed to the higher concentration SO2 was 73% and 74% of that of the control. The results indicated that SO2 inhalation may cause neurological damage in rat cerebral cortex through neuroinflammation and abnormity of signal transduction in neuronal cytoplasm and gene transcription in the nucleus.
出处
《应用与环境生物学报》
CAS
CSCD
北大核心
2015年第2期372-376,共5页
Chinese Journal of Applied and Environmental Biology
基金
国家自然科学基金项目(21377076)
山西省高等学校中青年拔尖创新人才项目(20120201)资助~~
关键词
二氧化硫
大脑皮层
胶质细胞
炎症因子
胞外信号调节激酶
环磷腺苷效应元件结合蛋白
sulfur dioxide
cerebral cortex
gliacyte
inflammatory cytokines
extracellularly regulated kinase 1/2
cAMPresponse element-binding protein
