NF-κB信号通路及自噬在十溴联苯醚暴露致神经毒性中的作用机制

It is reported that perinatal exposure to brominated flame retardants-brominated diphenly ethers-209(BDE-209) exhibited neurotoxicity and decreased learning and memory in offspring,but the specific mechanism was unknown.To investigate the neurotoxic mechanism of BDE-209 is the solution to prevention and control of disease induced by flame retardant pollution internationally.This study investigates the effects of BDE-209 on NF-κB signaling pathway and autophagy and cell function changes in nerve cells based on the theory that BDE-209 decreased learning and memory in offspring.We also investigated the effects of perinatal exposure to BDE 209 on the central nervous system in offspring to reveal the mechanism of neurotoxicity from overall level-the cellular level-the molecular level and to explore the role of NF-κB signal pathway and autophagy in the neurotoxicity.The present study is a question in the area of medicine which may provide a new evidence to clarify the possible mechanisms underlying the BDE-209-induced neurotoxicity.It may provide a new insight in treatment and drug screening of BDE-209 induced neurotoxicity,and provide the scientific basis for solving the sustainability of prevention of diseases induced by environmental pollution.

研究表明溴代阻燃剂—十溴联苯醚（BDE-209）围生期暴露具有神经发育毒性,会影响子代的学习记忆能力,具体机制不详,寻找BDE-209神经毒性机制是解决当前国际上流行的阻燃剂环境污染疾病防治的瓶颈与难点。本项目是基于目前BDE-209会影响子代的学习记忆能力的理论研究为基础,利用神经细胞研究BDE-209暴露后NF-κB信号通路及自噬的改变与细胞功能之间的关系,从整体水平-细胞水平-分子水平揭示妊娠期BDE-209宫内暴露后对子代神经细胞的毒性机理,探讨NF-κB信号通路及自噬在围产期BDE-209暴露后神经发育毒性的可能机制。本研究是一项医学科学领域的研究,这种探讨BDE-209神经毒性机制将为以后疾病治疗,药物筛选奠定理论基础,并且为解决我国环境污染疾病防治的可持续性研究提供相关科学依据。

本项目是基于目前十溴联苯醚（BDE-209）会影响子代的学习记忆能力的理论研究为基础,利用神经细胞研究BDE-209暴露后NF-κB信号通路的改变与细胞功能之间的关系,探讨NF-κB信号通路在围产期BDE-209暴露后神经发育毒性的可能机制。. 本研究中我们通过体外培养神经干细胞，并将它们暴露于不同的BDE-209浓度中，检测BDE-209暴露后NF-κB蛋白表达水平，同时检测了凋亡相关蛋白caspase-3和caspase-3酶蛋白，磷酸化细胞外信号调节激酶（ERK）和c-Jun N末端蛋白激酶（JNK）蛋白表达水平，进一步评估BDE-209对神经干细胞增殖及凋亡的影响及潜在的机制。我们的数据表明BDE-209在一定剂量和作用时间内可致海马神经干细胞的NF-kB蛋白表达增加，p-ERK1/2，p-JNK1/2表达未见明显改变，而且，BDE-209增加凋亡相关蛋白caspase-3和caspase-3酶蛋白表达水平，而NF-κB抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）可以减少BDE-209引起的凋亡相关蛋白的表达，推测BDE-209在一定浓度范围内可能通过NF-kB信号通路导致神经干细胞发生异常改变。. 本研究是一项医学科学领域的研究,这种探讨BDE-209神经毒性机制将为以后疾病治疗,药物筛选奠定理论基础,并且为解决我国环境污染疾病防治的可持续性研究提供相关科学依据。