纳米雄黄的急性毒性实验

Acute Toxicity of Nano-realgar

目的探索纳米雄黄对小鼠的急性毒性作用,为其临床应用提供依据。方法将60只小鼠随机分6组,每组10只。均采用灌胃给药：对照组给予0.5%羧甲基纤维素钠,其他组分别给予1031、515.5、257.8、128.8、64 mg·kg^-1的纳米雄黄混悬液;灌胃容积为25 ml·kg^-1。观察小鼠灌胃后毒性反应及死亡情况,Bliss法计算半数致死量（LD50）。对各组死亡小鼠及时解剖,取心、肝、脾、肺、肾进行病理检查。结果给药后,各组小鼠活动减少,不进食水,耳缘颜色变暗,呼吸急促,精神萎靡,眼球分泌物增加,粪便呈灰黑色。1031 mg·kg^-1组全部死亡,515.5 mg·kg^-1组死亡9只,257.8 mg·kg^-1组死亡2只,128.8 mg·kg^-1组死亡1只,64 mg·kg^-1组无死亡。用Bliss法计算LD50为309.72 mg·kg^-1,LD50（Feiller校正）的95%可信限为226.97~422.93 mg·kg^-1,LD5=137.36 mg·kg^-1,LD95=698.35 mg·kg^-1。死亡小鼠尸检观察,双肺、肝脏弥漫性充血,脾脏肿大发黑,小肠壁弥漫性充血,小肠胀气,部分肠道肿胀,发黑坏死。未死亡小鼠未见异常。结论小鼠灌胃给予纳米雄黄在64.4 mg·kg^-1时未见明显急性毒性反应;当剂量大于64.4 mg·kg^-1时,小鼠中毒现象会随着剂量的增大而增强。

Objective To explore the acute toxicity of realgar nano-particles in mice in order to facilitate its clinical application. Methods 60 mice were randomly and evenly divided into six groups that received intragastric administration. The control group was given 0. 5% sodium carboxymethyl cellulose while the other groups were given1031,515. 5,257. 8,128. 8,64 mg·kg^-1realgar nanometer suspension. The intragastric volume weight ratio was 25mg·kg^-1. To observe the toxic reaction and death rate of mice,we calculated the median lethal dose（ LD50） with Bliss method. The dead mice in each group were anatomized quickly,and their heart,liver,spleen,lung and kidney were taken out for pathological examination. Results The activity of the mice was reduced after administration,without eating or drinking,but with other symptoms,such as shortness of breath and increase of secretion of the eyeball.All mice died in the 1031 mg·kg^-1group,nine in 515. 5 mg·kg^-1group,two in 257. 8 mg·kg^-1group,and one in128. 8 mg·kg^-1group,but norne died in the 64 mg·kg^-1group. Calculated with the Bliss method,the LD50was309. 72 mg·kg^-1,with the 95% confidence limits（ Feiller correction） 226. 97- 422. 93 mg·kg^-1; LD5was137. 36mg·kg^-1,LD95 was 698. 35 mg·kg^-1. Autopsy showed diffuse congestion of the lung and liver,swelling and blackening of the spleen while the surviving mice remained normal. Conclusion No obvious acute toxicity symptoms are found in mice administrated with the 64. 4 mg·kg^-1dose of realgar nanoparticles,but when the dose exceeded64. 4 mg·kg^-1,the poisoning of mice will be intensified with the dose.