亚慢性暴露苯并芘对学习记忆相关神经递质受体基因表达的影响

Effect of sub-chronic Benzo(a)pyrene exposure on neurotransmitter receptor gene expression correlated of learning and memory

目的探索亚慢性苯并芘[B(a)P]暴露对学习记忆能力及大鼠海马组织中正常基因表达的影响。方法 24只SD大鼠随机分入空白对照组、溶剂对照组和B(a)P处理组(6.25 mg/kg),腹腔注射14周。采用Morris水迷宫实验(MWM)评价各组实验动物行为学表现,全基因组寡核苷酸芯片和PCR技术测定影响学习记忆能力的基因表达。DAVID分析富集基因本体(GO)和KEGG通路中表达基因的差异。结果水迷宫试验结果显示,B(a)P处理组较对照组逃避潜伏期时间明显增加,而跨过平台次数(8.26±1.14)次及目标象限停留时间(19.24±2.63)s明显降低(P<0.05)。基因芯片和PCR结果表明B(a)P暴露能影响神经递质受体mRNA的表达。基因本体和KEGG通路分析显示,受影响最为明显的基因本体类别是"行为",第四位的为"学习和记忆"。结论亚慢性B(a)P暴露可导致行为学改变,其改变与神经递质受体基因表达有关。

Objective To investigate the effect of sub-chronic Benzo （a）pyrene [ B （a）P ] exposure on learning and memory, and select candidate genes involving neurotransmitter receptor related to learning and memory. Methods 24Sprague-Dawly（SD） rats were randomly divided into blank control group, vehicle control group and B（a）P exposed group （6,25 mg/kg）, and rats were injected intraperitoneal for 14 weeks. Morris water maze （MWM） was used to evaluatebehavioralmanifestation among each group. Whole genome oligo microarrays and Polymerase Chain Reaction （PCR） were conducted to measure those genes expression impact on learning and memory. The web tool DAVID was used to analyze the significantly enriched gene ontology （GO） and KEGG pathways in differential expressed genes. Results The result of MWM demonstrated that, the escape latency in B （a）P exposed group was significantly higher compared with control groups, while the number of crossing the platform （8.26± 1.14） and the time spent in the target area （ 19.24±2.63）s were significantly decreased. Microarray and PCR results revealed that B （a）P exposure may have influence on mRNA expression of neurotransmitter receptors. GO and KEGG pathways showed that the most significantly affected gene ontology category wasbehavior, while learning and memory was the fourth significant affected by B （a）P.Conclusion Sub-chronicB （a）P exposure could induce behavior change, which may related to neurotransmitter receptor gene expression.