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目的研究农药百草枯(praquat,PQ)和代森锰(maneb,MB)单独和(或)联合暴露对小鼠黑质致密部(substanitial nigra compact,SNc)脑区多巴胺(dopamine,DA)能系统的影响,并探讨其与帕金森症(Parkinson’sdisease,PD)发病的关系。方法将120只健康清洁级5周龄昆明小鼠随机分为对照(生理盐水)组、PQ(5mg/kg)组、MB(15mg/kg)组、PQ(5mg/kg)+MB(15mg/kg)组,每组30只。采用腹腔注射方式进行染毒,染毒剂量为10ml/kg,每周染毒2次,连续染毒16周。采用爬杆试验和开阔试验检测小鼠运动行为的变化,对SNc区域进行组织病理学观察和神经元细胞计数。以荧光分光光度法检测纹状体(Caudateputamen,CPu)脑区中DA的含量。结果各组动物体重间比较,差异均无统计学意义(P>0.05)。染毒前和染毒8、16周后,各组小鼠的爬杆时间和跨格数间比较,差异均无统计学意义(P>0.05)。与对照组比较,染毒8、16周后PQ+MB组小鼠中脑SNc区神经元呈现胞体固缩样退化形态,细胞数量显著减少(P<0.01);而PQ组和MB组无显著性变化(P>0.05)。与对照组比较,染毒16周后第1天仅PQ+MB组小鼠纹状体脑区DA含量较高,差异有统计学意义(P<0.01);而PQ组和MB组小鼠纹状体脑区DA含量无显著性变化(P>0.05)。结论单独PQ或MB低剂量长期暴露对SNc脑区的神经元无影响,二者低剂量联合暴露可导致SNc神经元损伤和丢失,表明PQ和MB的协同神经毒性可能与帕金森症发病有关。
Objective To investigate the effects of pesticide praquat (PQ) and maneb (MB) alone and / or in combination on dopamine (DA) energy system in mouse brain substantiitized nigra compact (SNc) And to explore its relationship with Parkinson’s disease (PD). Methods 120 healthy Kunming mice of 5 weeks old were randomly divided into control (saline) group, PQ group (5mg / kg), MB group (15mg / kg) kg) group, 30 rats in each group. The rats were injected intraperitoneally with the dose of 10ml / kg twice a week for 16 weeks. The climbing motion test and the open test were used to detect the changes of the motor behavior of the mice. The histopathological observation and neuronal cell counting were performed on the SNc area. The content of DA in brain regions of Caudate putamen (CPu) was detected by fluorescence spectrophotometry. Results There was no significant difference in the body weight among all groups (P> 0.05). Before and 8 and 16 weeks after exposure, there was no significant difference in the climbing time and the number of grids between the mice in each group (P> 0.05). Compared with the control group, neurons in the SNc of midbrain of PQ + MB group showed degenerated cells in the pyknosis group after 8 and 16 weeks exposure (P <0.01), but no significant difference between PQ group and MB group Sexual changes (P> 0.05). Compared with the control group, DA content in striatum of mice in PQ + MB group was higher on the first day after exposure for 16 weeks (P <0.01), while PQ group and MB group There was no significant change in DA content in brain regions (P> 0.05). Conclusion Long-term exposure to low doses of PQ or MB alone has no effect on the neurons in SNc brain regions. The combined exposure of low dose and high dose of PQ or MB can lead to the damage and loss of SNc neurons, suggesting that the synergistic neurotoxicity of PQ and MB may be related to the pathogenesis of Parkinson’s disease.