苯并[a]芘神经毒作用及对小鼠脑组织热应激蛋白 70,90β水平的影响(英文)

Neurotoxicity of benzo[a] pyrene and its effects on heat stress protein 70 and heat stress protein 90β in brain tissue of mice

背景:苯并犤a犦芘代表的多环芳烃是一种广泛存在于生产和生活环境中的化学污染物,国外发现苯并犤a犦芘在一定条件下具有体外神经毒性。目的:研究苯并犤a犦芘对小鼠的神经毒性及对脑组织中两种热应激蛋白70,90β表达的影响。设计:以实验动物为研究对象的随机对照实验。单位:一所大学的热生物与分子毒理实验室及一所大学的预防医学系。材料:实验在华中科技大学同济医学院热生物与分子毒理实验室进行。将50只昆明种小鼠随机分为5组,10只/组,染毒组分为高、中、低3个剂量组,设溶剂对照及空白对照组。染毒组用苯并犤a犦芘植物油溶剂腹腔注射,高、中、低剂量组每次分别注射7.8,3.2和1.3mg/kg,4次/周。溶剂对照组用植物油溶剂作平行处理,空白对照组不做处理。方法:观察动物一般情况及神经系统表现,8周后取各组小鼠全脑组织,计算脑组织脏器系数,Westernblot法检测两种热应激蛋白70,90β水平。主要观察指标:苯并犤a犦芘染毒对小鼠脑组织热应激蛋白70及90β表达的影响。结果:①中、高剂量苯并犤a犦芘染毒组小鼠脑组织质量明显低于空白对照组(P<0.01,P<0.001),高剂量BaP染毒组小鼠脑组织脏器系数明显低于其他组(P<0.001)。②热应激蛋白70表达改变以低剂量苯并犤a犦芘染毒组相对表达值明显增高为特征;

BACKGROUND: Benzo[a]pyrene(BaP) is kind of polyaromatic hydrocarbon which is a chemical pollutant extensively existing in living and productive environments.I t is found overseas that it has neurotoxic effects under certain conditions. OBJECTIVE:To study the neurotoxicity of BaP and its effects on expression of t wo heat stress proteins(HSPs) HSP70 and HSP90βin brain tissue of mice. DESIGN:Randomized case control study of experimental animals. SETTING:Laboratory of thermobiology and molecular toxicology of a unversity,de partment of preventive medicine of a university. MATERIALS:The experiment was conducted in the Thermobiology and Molecular Toxi city Laboratory,Tongji Medical College,Huazhong Science and Technology Universit y.Fifty male Kunming mice were randomly divided into 5 groups with each of 10 mi ce including 3 administrated groups, 1 vehicle group and 1 control group.All mic e in 3 exposed groups were intraperitoneally administrated BaP dissolved in corn oil at dose levels of 7.8 mg/kg,3.2 mg/kg and 1.3 mg/kg respectively for four t imes per week.The mice in vehicle group received an equal volume of corn oil and the mice in control group received no additional treatment. METHODS:The signs of neurotoxicity in each group were examined and recorded du ring the administration. At the end of 8 week administration, the brains were e xcised to calculate brain tissue organ coefficient.Western blot method was used to assay the HSP70 and HSP90β. MAIN OUTCOME MEASURES:Effects of BaP on HSP70 and HSP90βin brain tissue of mi ce. RESULTS:①The mass of brain tissue in mice of middle and high dose of Bap expo sure groups was much lower than that of control group(P< 0.01,P< 0.001) while th e organ coefficient of high dose group was much lower than that of other groups( P< 0.001).②The expressive change of HSP70 was characterized by greatly increase d expression in low dose group while the relative expression of HSP90βwas incre ased in middle and high dose groups. CONCLUSION:BaP has certain neurotoxic effects. With the increase of toxic dose , the expression of HSP90βincreases which can be used as signal of toxic damage under certain conditions.