哈伯因对急性有机磷中毒神经损伤的保护作用研究

目的观察哈伯因(HupA)对急性水胺硫磷和辛硫磷中毒的神经病理改变和神经递质谷氨酸(Glu)和nNOS表达的影响。方法选取成年雄性昆明小鼠,分为3组:空白对照组、染毒组、HupA组,每组20只。染毒组和HupA组动物分别经口染毒水胺硫磷(14.7mg/kg)或辛硫磷(1702mg/kg),治疗组染毒前2h经口给予HupA(0.5mg/kg),空白对照组给予吐温-80。染毒24h后处死动物,取出大脑,按大脑冠状切面进行选块、切片,一部分做甲苯胺蓝染色;一部分进行免疫组织化学检查,供检测脑皮质、海马组织的Glu和nNOS使用。结果染毒组病理学检查尼氏小体数量减少,染色变浅,而HupA组尼氏小体改变明显减轻。水胺硫磷中毒小鼠脑组织中Glu阳性细胞减少(P<0.01),nNOS阳性细胞增多(P<0.01)。与染毒组比较,HupA组Glu阳性细胞面积显著增多(P<0.01),海马区nNOS阳性面积显著减少(P<0.01)。辛硫磷染毒组未见改变。结论 HupA对水胺硫磷急性中毒引起的神经损伤有一定得保护作用,对辛硫磷急性中毒引起的神经递质改变无显著影响。

Effect of Huperzine A on neural lesion of acute organophosphate poisoning in mice

Objective Effects of neurophathologic changes and expression of Glu and nNOS were observed in acute isocarbophos and phoxim poisoning in mice.Methods 60 KM male mice were randomly divided into three groups,which were control,non-treated and Huperzine A(HupA)-treated groups.The control group was given tween-80.Non-treated group was given isocarbophos(14.7mg/kg)or phoxim(1702mg/kg).HupA-treated group was given HupA 2h before phoxim or isocarbophos.Twenty-four hours after exposure,the whole brain was removed and adjacent coronal sections was obtained.One part of sections were stained with toluidine blue.The part of sections were used to assessed the expression of Glu and nNOS in the cortex and hippocampal of brain by immunohistochemistry.Results Compared to control group,non-treated group was observed nissal body nembers reduced and dyeing light.The animals of HupA protective group were observed nissal body nembers reduced,but the lesional degree was lighter obviously than non-treated group.The statistically reduced of the expression of Glu(P<0.01),the elevation of nNOS(P<0.01),after Isocarbophos intoxication were observed.Compared to non-treated group,the significant elevation of Glu(P<0.01) and reduced of nNOS(P<0.01) was observed on HupA-treated groups.Whereas for phoxim treatment,no changes were observed.Conclusion HupA have protective effect against glutamatergic systems disorder caused by Isocarbophos poisoning.Administration of HupA have no effects of the neurotransmitter changes induces by acute poisoning of phoxim.It is different for the toxic effect mechanism of the two organophosphate.