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目的 研究氯胺酮长期滥用模型中海马区半胱氨酸蛋白酶(caspase)3和突触后密度蛋白(PSD)95的表达变化.方法 每日小鼠腹腔注射氯胺酮(30 mg/kg)、持续3个月建立小鼠氯胺酮长期滥用模型,采用免疫组化及Western blotting检测小鼠氯胺酮长期滥用后caspase-3和PSD-95的表达情况.结果 免疫组化结果显示caspase-3表达增强,PSD-95表达减弱.Western blotting结果显示caspase-3活化片段蛋白表达升高,PSD-95蛋白表达下降.结论 氯胺酮长期滥用致小鼠脑海马区caspase-3表达增加、PSD-95表达减弱,这一结果揭示了长期滥用氯胺酮所致神经毒性作用的可能机制.“,”Objective To study the changes of hippocampal caspase-3 and PSD-95 expression levels in the mice exposed to ketamine 30 mg/(kg·d)for three months. Methods Forty C57BL/6 mice were randomly divided into two groups,and the chronic ketamine addiction model was established by giving mice a three month course of daily intraperitoneal injections of ketamine. Immunohistochemical study and Western blot-ting were applied to observe the expression of caspase-3 and PSD-95 protein. Results There were more expression of caspase-3 and less of PSD-95 in ketamine group as detected by immuohistochemistry. Western blotting results showed caspase-3 active fragment level significantly increased com-pared to saline group,but PSD-95 protein level was decreased. Conclusion The increased level of caspase-3 protein and reduced expression of PSD-95 are observed after long-term ketamine administration. These findings may provide an evidence for the neurotoxicity in mouse hippocampus of chronic ketamine addition as a recreational drug.