氯胺酮致小鼠产生类精神分裂症与NRG1、ErbB4 mRNA表达的相关性

The Correlation between Ketamine-induced Schizophrenia-like Signs in Mice and the Expressions of NRG1,ErbB4 mRNA

目的探讨氯胺酮连续给药致小鼠产生的类似精神分裂症症状,与精神分裂症易感基因神经调节蛋白1(neuregulin-1,NRG1)及其受体ErbB4 mRNA表达的相关性,为研究精神分裂症的可能发病机制提供参考依据。方法50只雄性昆明种小鼠,随机分为生理盐水组、氯胺酮小剂量(25 mg/kg)、中剂量(50 mg/kg)、大剂量(100 mg/kg)组和氯氮平治疗组,腹腔注射给药,1次/d,连续7 d。氯氮平组在连续腹腔注射7d氯胺酮(1次/d,每次100mg/kg)后,再用氯氮平灌胃7d(1次/d,每次20mg/kg)。HE染色观察海马神经元的变化;采用逆转录-聚合酶链反应(RT-PCR)检测海马中NRG1及ErbB4 mRNA的表达。结果注射7d氯胺酮后,大剂量组海马区NRG1及ErbB4 mRNA的表达显著减少。结论氯胺酮诱导小鼠产生类似精神分裂症的症状,可能与海马区NRG1及ErbB4 mRNA的表达减少相关联。

Objective To explore the correlation between signs similar to schizophrenia in mice after ketamine administration and the expressions of NRG1 and ErbB4 mRNA in order to explain the possible pathogenesis of schizophrenia. Methods Fifty KM mice were randomly divided into 5 groups which were administered in- traperitoneally with saline, elozapine and different dosages ketamine. The ketamine groups were administered intraperitoneally with low dosage（25 mg/kg）, middle dosage （50 mg/kg） and high dosage （100 mg/kg） one time every day for 7 days. After administration of 100 mg/kg ketamine for 7 days, the elozapine group was introgastrically administered 20 mg/kg with clozapine one time every day for 7 days. The pathological changes of hippocampus neurons were observed by HE stain. The expressions of the NRG1 and ErbB4 mRNA in hippocampus were detected by reverse transcriptase polymerase chain reaction （RT-PCR）. Results In the group with high dosage of ketamine, the levels of NRG1 and ErbB4 mRNA were significantly lower than that of the group with saline. Conclusion Ketamine may induce signs similar to schizophrenia in KM mice. The mechanism may be involved in the reduction of NRG1 and ErbB4 mRNA expression.