对氨基水杨酸钠对锰致神经炎症的干预机制

项目名称： 对氨基水杨酸钠对锰致神经炎症的干预机制

项目编号： No.81460505

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 姜岳明

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： 锰中毒病人不仅有锥体外系损伤的临床表现，也有丘脑损伤的症状和体征。我们的T1-加权磁共振成像（MRI）和氢质子磁共振波谱（1H-MRS）研究发现，锰冶炼工苍白球锰蓄积，丘脑及其邻近基底核γ-氨基丁酸(GABA)-感兴趣区 GABA水平明显增加，肌醇（mI）水平明显降低，后者可能是锰暴露引起神经胶质细胞损伤，且可能与神经炎症发生有关。我室率先应用对氨基水杨酸钠（PAS-Na）治疗锰中毒患者效果较好。本项目拟通过体内外毒理学研究和职业人群调查相结合的方法，采用免疫组化、高效液相色谱、单细胞凝胶电泳、酶联免疫吸附剂测定法、实时定量荧光PCR和蛋白质印迹法等技术探讨锰致大鼠丘脑神经元、神经胶质细胞损伤引起的神经毒性及PAS-Na的干预作用机制；探讨锰致大鼠丘脑炎症反应及PAS-Na的干预作用机制；探讨职业性锰暴露致工人神经炎症反应以及PAS-Na对中毒病人的治疗效果，为锰中毒防治工作提供科学依据。

中文关键词： 神经毒理学；神经毒性；对氨基水杨酸钠；锰中毒；神经炎症

英文摘要： Manganism patients not only had the clinical features of the extrapyramidal damage, but also had the signs and symptoms of the thalamus damage. Our findings from T1-weighted magnetic resonance imaging (MRI) and hydrogen proton magnetic resonance spectroscopy (1H-MRS) showed accumulated manganese level in globus pallidus, elevated gamma aminobutyric acid (GABA) and decreased myo-inositol (mI) levels in the thalamus and adjacent basal ganglia. The decreased myo-inositol (mI) level might be caused by manganese-induced damage of glial cells, which was associated with, nerve inflammation. The treatment of manganese poisoning patients with sodium para-aminosalicylic acid (PAS-Na) had firstly been applied by our department and this application had obtained a favourable effect. The research methods of in vivo and in vitro toxicology combined with case-control study, techniques of immunohistochemical staining, high performance liquid chromatography，single cell gel electrophoresis，enzyme-linked immunosorbent assay，real-time PCR and western blot will be used in the present project. The intervenient mechanism of PAS-Na on manganese neurotoxicity of the injuried neuron, glial cell in thalamus of the exposed rats will be explored. The intervenient mechanism of PAS-Na on manganese induced inflammation in thalamus of the exposed rats will be studied. The effect of nerve inflammation in occupational manganese-exposed workers and intervenient effect of PAS-Na on manganism patients will also be investigated. The present project will provide a scientific basis for prevention and treatment of manganese poisoning.

英文关键词： neurotoxicology;neurotoxicity;sodium para-aminosalicylic acid;manganism;nerve inflammation