氟虫腈对小鼠的急性毒性及药物治疗效果

An experimental study on acute poisoning by fipronil in mice and its pharmaceutical therapy

目的探讨氟虫腈对小鼠的急性毒性及地西泮和苯巴比妥钠的治疗效果。方法分别以6个剂量的氟虫腈灌胃染毒,观察急性中毒后小鼠行为改变、重要脏器的病理形态学改变及死亡情况;应用免疫组织化学和显微图像技术检测中毒小鼠大脑谷氨酸及γ氨基丁酸(γGABA)阳性神经细胞的分布和含量。小鼠经氟虫腈(90mg/kg)灌胃0.5h后腹腔注射地西泮和苯巴比妥钠,观察并比较各治疗组小鼠的死亡时间和生存率。结果各剂量组小鼠均出现抽搐等中枢神经系统兴奋症状;电镜下可见大脑海马区神经元细胞核膜间隙轻度扩张,神经胶质细胞空泡化,神经纤维呈脱髓鞘样改变;与对照组相比,氟虫腈急性中毒小鼠大脑皮质的谷氨酸平均阳性细胞数目(N)和阳性细胞面积比(Aa%)明显增加,但皮质和海马CA1区GABA阳性细胞的N和Aa%与正常组比较无明显差异。地西泮、苯巴比妥钠治疗后小鼠生存率均为58%。结论氟虫腈急性中毒小鼠主要表现为中枢神经系统兴奋症状,造成中枢神经细胞的损害,免疫组织化学提示该改变可能与中枢神经系统谷氨酸递质过度表达有关;早期应用地西泮、苯巴比妥钠对氟虫腈急性中毒小鼠有较好的治疗效果。

Objective To investigate the toxicity of fipronil in mice and the therapeutic effects of diazepam and phenobarbital sodium. Methods Mice were administered by gastric tube with fipronil at six doses and their behavioral changes, pathological changes in their major viscera under light and electron microscopy and deaths were observed after acute poisoning. Distribution and quantity of nerve cells positive in glutamic acid （Glu） or γ-aminobutyric acid （γ-GABA） in the brain of mice were detected by immunohistochemical methods and micro-image analysis. The time of death time and survival rate were observed and compared between the varied groups of mice injected intraperitoneally with diazepam and phenobarbital sodium, respectively, 0. 5 h after poisoning by fipronil at dose of 90 mg/kg. Results All the mice acutely poisoned by fipronil at varied doses showed some exciting symptoms in the central nervous system （CNS）, including convulsion. Nuclear membrane space slightly expanded, neuroglia cells vacuolized and nerve fiber demyelinated under electron microscopy. The number and area of ceils positive in Glu in the cerebral cortex of mice acutely poisoned by fipronil increased significantly, as compared to those in control mice. There was no significant difference in the number and area of ceils positive in γ-GABA in the hippocampal CA1 region between poisoned and normal control groups. Survival rate of mice treated with diazepam or phenobarbital sodium was 58 percent. Conclusion Mice with acute poisoning by fipronil appeared exciting symptoms in CNS, leading to damage in its nerve ceils.. Immunohistochemical techniques showed the damage could be related with the over-expression of glutamate transmitter in CNS. Early use of diazepam or phenobarbital sodium in treatment for acutely poisoned mice by fipronil could get better therapeutic efficacy.