【作者】 刘罗慧；

【导师】 赵玲玲；

【作者基本信息】 中南大学 ， 儿科学， 2008， 硕士

【摘要】 目的:研究新生鼠暴露亚中毒阈剂量毒死蜱(chlorpyrifos,CPF)诱导脑组织氧化损伤情况,探讨CPF导致神经发育毒性的作用机制。方法:出生11天SD大鼠108只,随机分为CPF组(n=36)、对照组(n=72)。对照组又分为溶媒二甲亚砜(Dimethysulfoxide,DMSO)对照组(n=36)和生理盐水(Normal Saline,NS)对照组(n=36)。大鼠出生后11-14天,连续经腹部皮下注射亚中毒阈剂量(以下简称“亚剂量”,5mg/kg.d)CPF,制作新生SD大鼠暴露亚剂量CPF动物模型,对照组分别以DMSO、NS替代CPF。所有大鼠在最后一次注药后12小时、24小时、72小时三个时间点分别被处死,并立即取脑,期间严密观察大鼠是否有急性有机磷农药中毒症状。用可见分光光度法测定脑组织匀浆超氧化物岐化酶(SOD)活性和丙二醛(MDA)含量变化;免疫组织化学和Western Blotting方法检测脑蛋白羰基表达变化情况。所有数据用均值±标准差((?)±S)表示,所有资料采用SPSS12.0统计软件包进行数据处理。结果:1.新生鼠暴露亚剂量CPF未见急性有机磷农药中毒症状。2.脑组织匀浆MDA含量发生改变,CPF组与两对照组比较,数值增高,差异有统计学意义(P＜0.05)。3.脑组织匀浆SOD含量发生改变,CPF组与两对照组比较,数值减少,差异有统计学意义(P＜0.05)。4.CPF组与对照组比较,脑组织蛋白羰基含量增加。特别是免疫组织化学方法检测下丘脑层面,差异有统计学意义(P＜0.05)。结论:1.新生鼠暴露亚中毒阈剂量CPF可诱导脑组织氧化损伤;2.氧化应激是CPF导致神经发育毒性的作用机制之一。更多还原

【Abstract】 Objective: To explore the oxidative damage effects on postnatal rats exposed to subthreshold doses of chlorpyrifos and the mechanisms of CPF caused development neurotoxicity.Methods: Postnatal 11 days SD rats (n = 108) were randomly divided in to CPF group (n = 36) and control group (n = 72).The control group were then further divided into dimethysulfoxide (DMSO, n = 36) group and normal saline group (NS, n = 36). Postnatal 11-14 days rats were injected with CPF at subthreshold doses for overt systemic toxicity (5 mg/kg/day). The control groups were injected the same doses of DMSO or saline instead. The animals were sacrificed respectively at 12 h, 24 h and 72 h after the final injection and the brains were collected immediately. The Acute organophosphorus pesticide intoxication symptom of the rats was monitored at the above three time points. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the rat brain homogenate were detected by spectrophotometry. Immunohistochemistry assay and Western Blotting assay were taken to detect the expression of protein carbonyl. All data were expressed as the mean±SEM. All data were analyzed using statistic software SPSS v12.0.Results:1. Exposed to subthreshold doses of CPF did not produce any acute organophosphorus pesticide intoxication symptoms.2. The content of MDA in the rat brain homogenate was changed. The CPF group had more MDA than the control groups (p<0.05).3. The content of SOD in the rat brain homogenate was changed. The CPF group had less SOD than the control groups (p<0.05).4. The CPF group had more protein carbonyl than the control group, especially in the hypothalamus detected by the Immunohistochemistry assay. There was significant difference (p<0.05).Conclusions: 1. Exposed to subthreshold doses of chlorpyrifos on postnatal rats can cause oxidative damage;2. Oxidative stress is one of the mechanisms of CPF caused development neurotoxicity.更多还原