【作者】 邢厚娟；

【导师】 徐世文；

【作者基本信息】 东北农业大学 ， 临床兽医学， 2007， 硕士

【摘要】 本文以有机污染物硝基苯(NB)为研究对象，以乙酰胆碱酯酶(AChE)、乙酰胆碱(ACh)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)、总抗氧化能力(T-AOC)、蛋白质羰基含量、病理学变化和细胞色素P450酶系为指标，研究了NB对小鼠肝、脑、脾、肾的毒性和抗氧化防御系统的损伤作用，并对其毒性作用机理进行了初步探讨，为全面评价NB对哺乳动物的生态毒理效应提供科学依据。研究结果表明：1．通过蓄积试验，证明NB的毒性属中度蓄积。2．通过显微和超微结构的观察，证明NB能够导致小鼠肝、脑、脾、肾各组织发生损伤，使其生理机能降低。不同剂量NB染毒后，病理组织结构变化的差异为判断和分析NB中毒效应提供了充分的形态学依据。3．NB能够诱导小鼠肝、脑、脾、肾各组织发生氧化应激，导致CAT、GSH-Px、SOD活性及T-AOC降低、MDA含量蛋白质羰基含量升高，破坏机体抗氧化防御系统及消除自由基功能，造成小鼠各组织发生氧化损伤，影响其正常的生理机能。4．随着染毒时间的延长和剂量的加大，小鼠脑乙酰胆碱酯酶活性不断降低，肝乙酰胆碱含量总体呈升高趋势，并表现为明显的剂量和时间依赖性，说明NB对神经递质乙酰胆碱产生了作用，表明其具有神经毒性。5．通过对小鼠肝脏内混合功能氧化酶活性的检测，证实NB能诱导细胞色素P450酶系中的b5、氨基吡啉-N-脱甲基酶、7-乙氧基香豆素脱烃酶(EROD)、和7-乙氧基香豆素O-脱乙氧基酶活性；抑制NADPH-cyc还原酶活性，近而影响机体正常的生理机能。综上所述，NB可以造成肝、脑、脾、肾组织的病理学损伤，抑制肝内混合功能氧化酶的活性，诱导氧化应激，影响组织酶活性，破坏机体抗氧化防御系统及清除自由基功能，引起机体蛋白质氧化损伤，进而发挥其毒性作用。更多还原

【Abstract】 This paper selected contaminant nitrobenzene (NB) as research object, studied its nervetoxicity and the damage on oxidize defend system on mice with acetylcholinesterase(AChE),catalase(CAT), acetylcholine(ACh), glutathion peroxidase(GSH-Px),erythrocuprein(SOD),malonaldehyde(MDA), Total antioxidant capacity(T-AOC), proteincarbonyl content、change ofpathology, and cytochromeP450 at the molecular level of toxicity. Moreover, this paper tried toprobe into the effect mechanisms of its toxicity and oxidation damage in liver,kdeny,brian,spleen,which provided the basis for the fully estimate of ecological toxicology on mammals. The resultsshowed:1. Certified that NB belong to midrange accumulation by cumulative test.2. Observation of ultrastructural and show minute points, verified that NB can damage the ratliver, brain, spleen, kidney and degrade physiological functions. As judge and analyze toxicosiseffect, variance of pathology organization has offered sufficient morphology proof, after usedifferent dosage of NB.3. NB can induce rat liver, brain, spleen, kidney and other tissue oxidative stress, degradeactivity of CAT, GSH-Px, SOD and T-AOC, content of protein carbonyl and MDA higher, damageantioxygen defence system and function of clean up free radicle, and make tissues oxidativedamage, impact their normal physiological functions.4. With time prolonging and dosage adding, the activity of acetylcholine esterase in mousebrain containing degrade, content of liver acetylcholine to step up, and to show time and dosagedependence apparentely. It demonstrate that NB make effect on neurotransmitter and acetylcholine,and have neurotoxicity.5. By the detection of mixed function oxidase activity in rat liver, prove that NB can induce b5,Aminopyrine-N-demethylase,ethoxyresorufin-O-deethylase(EROD),Coumarin7-hydroxylation, incytochromeP450 enzyme system; abaissement NADPH-cytochrome C reductase, contributionorganism normal physio-function.NB can make liver, brain, spleen and nephridial tissue pathology damage, to refrain theactivity of liver mixed function oxidase, induce oxidative stress, effect tissue enzymatic activity,destroy organism antioxygen defence system and function of clean up free radical, to cause proteinoxidation damage, to educe toxic action.更多还原