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题名 II-型拟除虫菊酯类农药对小鼠中枢神经系统毒作用机制的研究
姓名 柴晓静
院系 公共卫生学院
专业 劳动卫生学
学位名称 医学硕士
外文题名 THE STUDY ON THE CENTRAL NERVOUS TOXICITY OF II- PYRETHRINS IN MICE
第一导师姓名 王振全
关键词 Ⅱ-拟除虫菊酯;小鼠;脑;单胺类递质;氧化损伤;凋亡;bcl-2;p53
外文关键词 mice; brain;II-pyrethroid;monoamine neurotransmitters;oxidative damage;apoptosis;bcl-2; p53
学科 医学
摘要 目的 拟除虫菊酯类农药是70年代迅速发展起来的新型农药,最初是在除虫菊这种植物中提取出来的。拟除虫菊酯根据化学结构的不同可以将其分为两种类型:I型,不含α-氰基,以氯菊酯为代表;Ⅱ型,含α-氰基,以氯氰菊酯和溴氰菊酯为代表。由于拟除虫菊酯类农药具有高效、广谱、低毒、低残留的优点,已广泛用于农、林害虫、公共场所害虫和家庭害虫的防治,但是人们发现它对于中枢神经具有损伤作用,这一点已经引起了人们的重视 ,但是具体的作用机理到目前为止还没有彻底阐明。本课题观察II-型拟除虫菊酯类农药对昆明小鼠行为和体重的影响,小鼠脑内单胺类递质含量、小鼠脑的氧化损伤作用、小鼠脑细胞的促调亡作用以及对bcl-2和p53基因表达的影响,以探讨II-型拟除虫菊酯类农药对中枢神经系统的毒性作用及其机制。 方法 本研究采用慢性毒性试验将210只昆明系小鼠(雌雄各半)随机分为7组(每组30只),分别为溴氰菊酯(DM)1.8mg/kg组﹑2.7mg/kg组、3.6mg/kg组;氯氰菊酯(CP)4.0mg/kg组﹑6.0mg/kg组、8.0mg/kg组及色拉油对照组。小鼠于室温为(20±5)℃﹑24h自由光照条件下饲养,自由饮水进食,每日固定上午9时灌胃染毒,连续染6d停染一天。观察在实验期间,各组小鼠的行为及体重变化。连续30d经口灌胃染毒以后小鼠在禁食、但自由饮水24h后颈椎脱臼处死。取全脑,精确称重,高效液相色谱(HPLC)荧光检测法分别检测小鼠全脑中多巴胺(DA),去甲肾上腺素(NE),5-羟色胺(5-HT)的含量;检测DM、CP对小鼠脑中丙二醛(MDA)、羟自由基(-OH)、总抗氧化能力(T-AOC)、谷胱甘肽过氧化物酶(GSH-PX)活性的影响;采用免疫组化的方法分别检测小鼠脑中bcl-2和p53蛋白表达的变化。 结果 1.Ⅱ-型拟除虫菊酯对小鼠行为、体重及脏器系数的影响:各染毒组小鼠均出现不同程度撕咬和攻击等兴奋和刺激症状,且DM组较CP组程度严重,高剂量组较低剂量组严重。染毒组小鼠的体重增长较对照组缓慢,并且肝脏和脾脏的脏器系数与对照组比较有不同程度的升高,脑的脏器系数与对照组比较有不同程度的下降。 2.Ⅱ-型拟除虫菊酯对小鼠脑内单胺类递质含量的影响:六个染毒组小鼠脑内去甲肾上腺素(NE)、多巴胺(DA)含量与对照组相比均有不同程度的下降,而且存在剂量效应关系;但染毒组小鼠脑内5-HT的含量与对照组比较没有明显的变化;并且,Ⅱ-型拟除虫菊酯对实验小鼠脑内褪黑素(MT)的含量也有影响,染毒组小鼠与对照组相比MT含量明显降低。 3.II-型拟除虫菊酯对小鼠中枢神经系统氧化应激的影响:六个染毒组小鼠脑内丙二醛(MDA)和羟自由基(-OH)含量与对照组相比均有不同程度的升高,总抗氧化能力(T-AOC)和谷胱甘肽过氧化物酶(GSH-PX)的活性与对照组相比均有不同程度的下降,而且除了-OH以外,其余三个指标均存在剂量效应关系。 4.bcl-2和p53在II-型拟除虫菊酯诱导神经细胞凋亡机制中的作用:染毒组小鼠脑内bcl-2蛋白的表达与对照组相比有不同程度的下降,而p53蛋白的表达与对照组相比有不同程度的升高。 结论 长期低浓度接触DM和CP可以影响实验小鼠行为及体重;使脑内单胺类递质以及褪黑素的含量...
外文摘要 OBJECTIVE: Pyrethrins is a new type pesticide that had developed rapidly in 1870s. It was refined from the plant at first. It can be divided into two types from its chemical structure:The type I has non-alpha-cyano which is represented by permethrin; The II contains alpha-cyano which is represented by deltamethrin and cypermethrin. Due to theirs high efficiency, broad-spectrum, low toxicity and low-residue advantages, they have been widely used to control pests in agriculture, forests, public places and in household. It was found that it is harm to people for its central nervou system toxicity,but the specific mechanism has not been thoroughly explained. This study is mainly to observe effects of II-pyrethroid pesticide on content of monoamine neurotransmitters in the brain in mice , the oxidative damage in mice'' brain, the apoptosis in the mice'' brain cells and the effects of protein expression of bcl-2 and p53. So that to explore toxicity of II-pyrethroid pesticide and injury mechanism of mice in central nervous system. METHODS:We used the chronic toxicity tests, and 210 Kunming mice were randomly divided into seven groups respectively (n=30). Deltamethrin (DM) 1.8mg/kg group, 2.7mg/kg group and 3.6mg/kg group, Cypermethrin (CP) 4.0mg/kg group, 6.0mg/kg group, 8.0mg/kg group and the salad oil control group.The changes of mice'' weight and behaviour in every groups was observed in the periods of experiment.After treated by oral gavage for 30 days, the mice were fasting but drinking water free. 24 hours later, they were killed by cervical dislocation. The whole brains were peeled off, and weighted accurately. The fluorescence detect system of HPLC was used to detected content of Dopamine (DA), Norepinephrine (NE) and 5-Hydroxytryptamine (5-HT) in mice brain. And then we detected the effects of DM, CP to Maleic Dialdehyde (MDA),Hydroxyl radical (-OH),total antioxidant capacity (T-AOC) and Glutathione peroxidase (GSH-PX) activities in theirs brains. The immunohistochemical methods were used to detect the expression of bcl-2 and p53 in male mice brain. RESULTS: 1 Effects of II-type pyrethroids on mice'' pyrethroids, weight and organ coefficient: all the mice had tearing attacks, excitement and stimulation symptoms in varying degrees. And the DM groups were serious than the CP groups, while in the high dose groups were also serious than the low dose groups. The weight growth in the toxic groups were slower compared with the control group, and organ c...
研究领域 工业毒理
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