丙烯酰胺对神经丝的影响规律及其分子机制

项目名称： 丙烯酰胺对神经丝的影响规律及其分子机制

项目编号： No.30872088

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 于素芳

作者单位： 山东大学

项目金额： 31万元

中文摘要： 【背景】ACR是一种广泛应用的工业毒物，ACR中毒神经病病理特征是轴突NF异常增多、堆积，然而其机制不清。【目的】阐明NF改变的分子机制和寻找ACR暴露者健康监护指标。【方法】用分子生物学和生化实验技术方法相结合，通过动物实验研究ACR对NF三个亚单位的影响，进一步从NF基因表达和NF降解有关的钙离子、Calpain等方面探索NF改变的可能机制和作用环节；利用现场ACR暴露工人血清相关指标研究探索可能的生物效应标志物。【结果】 动物实验显示ACR可改变脊髓和坐骨神经NF水平；NF改变与Ca2+、mRNA、Calpain活性、CaMKⅡ#12289;PKA、PKC、CaM、cAMP、CaMKⅡ#12289;CDK5 、P35、P25有关。人群研究显示ACR暴露工人的NSE、Ca2+ 、Calpain、GSH-Px、MDA明显改变，且与皮肤污染相关密切。【结论】ACR 神经病与神经组织NF改变有关；NF改变与决定合成的NF mRNA 有关，也与参与分解的Ca2+、Calpain等有关；脊髓和坐骨神经NF改变趋势相反；ACR暴露工人的NSE、Ca2+ 、Calpain、GSH-Px、MDA变化与皮肤污染负荷相关。

中文关键词： 丙烯酰胺；神经丝；Calpain；钙离子；神经病

英文摘要： 【Background】 ACR is a neurotoxic material which was widely used in industries and can induce neurodegeneration. NF protein aggregation is a pathological hallmark of the neuropathy. However, the mechanisms of NF alteration at the nerves have not been completely elucidated.【Purpose】To explain molecular mechanism of NF in ACR axonopathy and find the health monitoring index of ACR exposure workers.【Methods】This study combined animal model and humans investigation by molecular biological and biochemical techniques to research the possible mechanisms in NF protein change. NFs and related indexes(Ca2+,Calpain,PKC,PKA,CaM,cAMP,CDK5,CaMKⅡP35 and P25) determination in ACR poisoning rat model. The possible nerve biological effect index were explored in ACR exposure workers.【Results】 The animal results show that NFs have changed in nerve tissues.The NF change related to Ca2+,Calpain,MDA,PKC,CaM,cAMP,CaMKⅡCDK5,P35 and P25. The change of NSE,Ca2+ ,Calpain，GSH-Px and MDA in serum of ACR exposure workers related to skin ACR load.【Conclusions】ACR neuropathy related to NFs change. NFs change not only related to NF production factor(NF mRNA), but also NF degeneration factors(Ca2+,Calpain etc.). It is contrary on NFs change between sciatic nerve and spinal cord. The change of NSE,Ca2+ ,Calpain，GSH-Px and MDA in serum of ACR exposure workers related to skin ACR. The results are very important to construct prevention strategy for the ACR exposure people and can supply the scientific data on the health survillence.

英文关键词： Aacrylamide; Neurofilament; Calpain; Calcium; Neuropathy