慢性有机磷中毒致大鼠认知功能障碍模型

目的探索氧乐果染毒建立大鼠慢性有机磷中毒认知功能障碍模型的合理给药方式和剂量。方法经学习记忆训练筛选的Wistar大鼠按染毒给药方式分为灌胃组和皮下注射组(均n=40),两组再分别分为①灌胃对照组或皮下注射对照组(均给予生理盐水);②灌胃氧乐果小剂量组和皮下注射氧乐果小剂量组(均给予氧乐果2.5 mg·kg-1·d-1);③灌胃氧乐果中剂量组和皮下注射氧乐果中剂量组(均给予氧乐果5 mg·kg-1·d-1);④灌胃氧乐果大剂量组和皮下注射氧乐果大剂量组(均给予氧乐果10 mg·kg-1·d-1)。各组均n=10。观察染毒期间大鼠一般状态、存活情况和记忆再现能力;苏木精-伊红染色观察各组大鼠海马和肝脏形态结构变化。结果①各氧乐果染毒组均有轻微中毒症状,灌胃氧乐果大剂量组和皮下注射氧乐果大剂量组最显著,灌胃氧乐果中剂量组和皮下注射氧乐果中剂量组次之,灌胃氧乐果小剂量组和皮下注射氧乐果小剂量组中毒不明显;②灌胃氧乐果大剂量组大鼠死亡7只(存活率30%)、皮下注射氧乐果大剂量组死亡5只(存活率50%),不宜用于造模;③记忆再现测试:各染毒组大鼠记忆保持能力有不同程度的降低,皮下注射氧乐果中剂量组造模效果较理想;④肝变性细胞指数分析:皮下注射氧乐果低剂量组对肝脏损伤最轻;⑤海马变性细胞指数分析:灌胃氧乐果大剂量组和皮下注射氧乐果大剂量组海马细胞损伤最重,死亡率较高。以皮下注射氧乐果中剂量组为宜。结论皮下注射氧乐果5 mg·kg-1·d-1是建立大鼠慢性有机磷中毒认知功能障碍模型的理想方法之一。

The Cognitive Impairment Models Induced by Chronic Poisoning of Organophosphate Inrats

Aim To explore the reasonable administration way and dose of omethoate in the establishment of cognitive impairment model induced by chronic organophosphate poisoning on rats.Methods After learning and memory training,qualified Wistar rats （80 in total）,according to the administration way,were divided into gavage group （n=40） and subcutaneous group （n=40） randomly.Then the two groups were respectively divided as following groups：① Gavage or subcutaneous control group （normal saline）; ② Gavage or subcutaneous with low dose omethoate group （2.5 mg·kg-1.d-1）; ③ Gavage or subcutaneous with moderate dose omethoate group （5 mg.kg-1d-1）; ④ Gavage or subcutaneous with large dose omethoate group （10 mg.kg-1d-1）,with 10 rats in each group.Results ① Rats in each exposure group showed mild poisoning symptoms.The poisoning symptoms of rats in gavage and subcutaneous with large dose omethoate groups were most obvious,followed by gavage and subcutaneous with moderate dose omethoate groups and mildest in gavage and subcutaneous with low dose omethoate groups.②Gavage and subcutaneous with large dose omethoate groups were not suitable to the establish models for their low survival rate,7 rats died in the former group with survival rate of only 30% and 5 rats died in the latter group with survival rate of 50%.③ The results of the memory reappearance test showed that the memory keeping ability （MKA） of rats in each exposure group declined at different degrees,and rats in subcutaneous with moderate dose omethoate group （5 mg·kg-1·d-1） were more obviously.④ The denatured cell index （DCI） of liver indicated subcutaneous with low dose omethoate group did the slightest harm to liver.⑤ The DCI of hippocampus showed that the hippocampus damage in gavage and subcutaneous with large dose omethoate groups was the most serious,but given the high mortality rate of the two groups,subcutaneous with moderate dose omethoate group （5 mg·kg-1d-1） was most suitable for the establishment of models.Conclusion Subcutaneous injection with 5 mg·kg-1·d-1 omethoate each day was one of the most reasonable method to establish cognitive impairment model induced by chronic organophosphorus poisoning in rats.