丙烯酰胺和2,5-己二酮对大鼠薄束核病理改变的差异性影响

Differential effects of acrylamide and 2,5-hexanedione on pathological changes of gracile nucleus in rats

目的:探讨神经毒素丙烯酰胺(AA)和2,5-己二酮(2,5-HD)对大鼠薄束核病理改变的差异性影响及其可能的机制。方法:将6周龄雄性SD大鼠随机均分为对照组、AA组、2,5-HD组,AA组和2,5-HD组分别腹腔注射AA和2,5-HD 10周建立亚急性中毒模型,对照组注射等体积生理盐水。免疫组织化学方法检测大鼠体质量、步态和旷场的行为学变化;取薄束核节段脑组织行冰冻切片,用烟酰胺腺嘌呤二核苷酸磷酸黄递酶(NADPH-d)组织化学方法检测一氧化氮合酶活性,用免疫组织化学方法检测胶质纤维酸性蛋白(GFAP)和降钙素基因相关肽(CGRP)的表达。结果:与对照组相比,2个毒素组大鼠体质量增长均受到抑制,并出现步态评分异常,活动能力下降。AA组薄束核区NADPH-d阳性神经元增多,2,5-HD组NADPH-d阳性神经退行性结构增多。2个毒素组薄束核GFAP表达均增多,CGRP表达无明显变化。结论:AA可导致薄束核区炎症反应;2,5-HD引起神经细胞代谢异常,并加速薄束核区出现神经退行性改变。

Objective:To investigate the differential effects of neurotoxin acrylamide(AA)and 2,5-hexanedione(2,5-HD)on the pathological changes of gracilis nucleus in rats and its possible mechanism.Methods:Six-weekold male SD rats were randomly divided into control group,AA group and 2,5-HD group.AA and 2,5-HD were injected intraperitoneally and seperately in AA group and 2,5-HD group for 10 weeks to establish subacute poisoning model.The same volume of normal saline was injected in the control group.The behavioral changes of body weight,gait and open field of rats were detected.and the brain tissues of gracile nucleus were taken for frozen sections.Activity of nitric oxide synthase was examied by nicotinamide adenine dinucleotide phosphodiaphorase(NADPH-d)histochemistry.Expression of glial fibrillary acidic protein(GFAP)and calcitonin gene related peptide(CGRP)was detecded by immunohistochemistry.Results:Compared with the control group,the increasing of body mass in the two toxin groups was inhibited,the gait score was abnormal and the ability of actions decreased.The number of NADPH-d positive neurons in the gracile nucleus was increased in the AA group,and the number of NADPH-d positive neurodegenerative structures increased in 2,5-HD group.The expression of GFAP in the gracile nucleus of the two toxin groups increased,but the expression of CGRP had no significant change.Conclusion:AA can lead to inflammation in the gracile nucleus area.2,5-hexanedione causes abnormal metabolism of nerve cells and accelerates the neurodegenerative changes in the gracile nucleus area.