百草枯和代森锰联合染毒对大鼠黑质纹状体系统的影响

目的 观察百草枯(paraquat,PQ)和代森锰(maneb,MB)联合染毒对大鼠运动行为和黑质纹状体系统神经元形态及电活动的影响,以探讨这两种农药与帕金森病(Parkinson's disease,PD)发病的关系.方法 37只大鼠随机分为对照组(11只)、PQ组(PQ 10mg/kg,13只)、PQ(10mg/kg)和MB(30 mg/kg)联合染毒组(PQ+MB组13只),每周2次腹腔注射,染毒6周,观察动物在斜板试验、网格试验和开阔试验中运动行为的变化情况;HE染色观察黑质神经元形态;利用细胞外电生理学方法记录纹状体神经元自发电活动.结果 与对照组或同组染毒前比较,PQ组及PQ+MB组大鼠从斜板上下滑次数增加,在网格上移动潜伏期延长,在开阔试验中自发运动减少,差异均有统计学意义(P＜0.05或P＜0.01).染毒后PQ组及PQ+MB组大鼠黑质致密部神经元出现受损形态改变,PQ组及PQ+MB组细胞密度分别为(82.17±12.91)和(41.15±6.44)个/mm2,与对照组[(143.10±20.85)个/mm2]比较,差异有统计学意义(P＜0.01).PQ组纹状体神经元的平均放电频率为(5.97±7.30)Hz,PQ+MB组为(6.95±9.87)Hz,较对照组[(1.78±5.05)Hz]明显提高,差异均有统计学意义(P＜0.01);PQ+MB组神经元混合簇状放电比例(22.3%)较对照组(9.8%)和PQ组(5.6%)明显增加,差异有统计学意义(P＜0.05,P＜0.01).结论 MB能加重PQ对大鼠黑质纹状体系统的损伤效应,表明这两种农药的协同毒性作用与PD发病相关联.

Abstract：

Objective To investigate the effects of exposure of paraquat and maneb on the behavior,the morphology and electrical activity of the Substantianigra and striatum, and to discuss the relationship between this two pesticides and Parkinson's disease. Methods 37 rats were divided randomly into 3 groups:control group(n=11 ), paraquat ( 10 mg/kg) group (n=13) and combinative group of paraquat ( 10 mg/kg) and maneb(30 mg/kg)(n= 13 ), and were exposed twice a week for 6 weeks by intraperitoneal injection. The behavior of animals in the declined-plane, the vertical-grid and the open-field test were observed. The morphology of substantia nigral neurons were investigated by HE pathology. The spontaneous discharge of striatum neurons were recorded after exposure. Results Compared to the control group and the pre-exposure group, both the numbers of animals sliding down from the declined-plane and the latency of rats' moving on the vertical-grid significantly increased, and the animals' autonomic movement decreased significantly (P＜0.05,P＜0.001). After the combinative exposure, the neurons of the Substantial nigra pars compacta (SN Pc ) were progressively impaired, the cell density of the paraquat group [(82.17±12.91 ) n/mm2] and the combined group [(41.15±6.44 )n/mm2] were lower than that in control group( 143.10±20.85 n/mm2) (P＜0.01). In the paraquat group(5.97±7.30 Hz) and the combined group [(6.95±9.87 ) Hz], the average discharge rates of the striatum neurons were increased significantly compared to the control group [( 1.78±5.05 ) Hz] (P＜0.01).The bursting discharge was increased significantly in the combined group(22.3% ) compared to the control group(9.8% ) and the paraquat group (5.6%) (P＜0.05,P＜0.01). Conclusion The co-exposure of paraquat and maneb could induce similar symptoms to Parkinsonism syndrome of rats such as rigidity, moving reduction and etc, and the combined exposure had a certain enhanced effect compared to alone paraquat exposure. The combinative exposure of paraquat and maneb could cause neural loss in SNPc and it is involved with the enhanced electrophysiological activity in striatum. The synergy toxicity of paraquat and maneb in nigrostriatal system is related to Parkinson's disease.     

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