成年小鼠氯胺酮慢性注射后行为改变以及海马CA3区小清蛋白和c-Fos的表达  

The effect of chronic ketamine injection on the change of behavior and expressions of PV and c- Fos in hippocampal CA3 in mice

作　　者：陈梅[1,2] 刘阳[2] 张志龙[3] 王德广[1] 

机构地区：[1]徐州医学院解剖学教研室,江苏徐州221002 [2]徐州医学院神经生物学实验中心,江苏徐州221002 [3]济宁医学院附属医院麻醉科,山东济宁272051

出　　处：《徐州医学院学报》2012年第5期299-302,共4页Acta Academiae Medicinae Xuzhou

基　　金：基金项目：济宁市科技发展（医学）计划项目（2009-56）

摘　　要：目的 观察小鼠氯胺酮慢性中毒产生精神分裂症样症状后,海马CA3区小清蛋白（parvalbumin,PV）和c-Fos蛋白的表达.方法 将60只成年昆明小鼠随机分为生理盐水组（NS）和氯胺酮给药组：50 mg/kg（K1）、100 mg/kg（K2）和150 mg/kg（K3）.每5天腹腔给药1次,连续注射6次,于给药完成后第5天,观察刻板行为和旷场实验的行为改变;免疫组织化学方法检测海马CA3区PV和c-Fos蛋白的表达.结果 与生理盐水组相比,给药组小鼠刻板行为和旷场实验得分明显增加（P〈0.01）,随剂量增加而递增;海马CA3区PV的表达低于生理盐水组,随剂量增加而递减,以K2、K3组差异有统计学意义（P〈0.01）;海马CA3区c-Fos的表达低于生理盐水组,随剂量增加而递减（P〈0.05）.结论 氯胺酮慢性中毒后,成年小鼠可产生精神分裂症样症状;海马CA3区PV和c-Fos蛋白的表达受抑制,随药物剂量的增加逐渐减少,可能与小鼠氯胺酮慢性中毒后产生精神分裂症样症状有关.Objective To observe the expressions of parvalbumin （PV） and c - Fos in hippocampal CA3 in mice after they showed symptoms similar to schizophrenia induced by chronic ketamine administration. Methods Sixty adult Kunming mice were randomly divided into the control group of saline （NS） injection and the three groups of ketamine injection including 50 mg/kg （KI）, 100 mg/kg （K2） and 150 mg/kg （K3）. The mice were administered by intraperito- neal injection once every five days for 6 times. Then stereotyped behavior was observed and the open field test was performed after 5 days from the last injection. The expression of PV and c - Fos in hippoeampal CA3 of mice were detected by immunohistochemica] staining in different groups. Results Compared to the control group, the scores of stereotyped behavior and open field test of ketamine groups increased significantly （ P 〈 0.01 ） , and tended to increase with the increasing dosage of ketamine. The expressions of PV in hippocampal CA3 were lower than that of the control group, and presented a negative correlation with the dosage of ketamine, with significant difference between K2 group and K3 group （P 〈0.01 ）. The expressions of c- Fos in hippoeampal CA3 were lower than that of the control group, and presented a negative correlation with the dosage of katamine （ P 〈 0.05 ）. Conclusion The adult mice can show symptoms similar to schizophrenia induced by chronic ketamine administration. The expressions of PV and e - Fos are suppressed with the in- creasing ketamine dosage, which may be related to the symptoms similar to schizophrenia induced by chronic ketamine poisoning.

关 键 词：精神分裂症样症状 行为 氯胺酮 小清蛋白 c—Fos 

分 类 号：R749.3[医药卫生—神经病学与精神病学]