氯胺酮致小鼠精神分裂样症状及其机制探讨

目的观察氯胺酮致小鼠精神分裂样症状,血清肌酸激酶（CK）、一氧化氮（NO）的改变,及对额叶MEK1 mRNA、ERK2 mRNA表达的影响。方法将40只昆明小鼠随机分为生理盐水组和氯胺酮小、中、大剂量4组。腹腔注射7d后观测行为学改变,用紫外分光光度法测定血清CK和NO水平,用RT-PCR方法检测额叶MEK1、ERK2的表达。结果与生理盐水组相比,给药组小鼠在行为学指标上有明显改变,以大、中剂量组显著,差异有高度统计学意义（P〈0.01）;各给药组小鼠血清CK活性均有不同程度增高,但仅大剂量组的差异有高度统计学意义（P〈0.01）,血清NO含量均显著增高,差异均有高度统计学意义（P〈0.01）;额叶MEK1的表达,中剂量组和大剂量组均明显下调,ERK2的表达在大剂量组明显下调,差异均有统计学意义（P〈0.05或〈0.01）。结论氯胺酮增加了小鼠血清CK活性和NO含量,抑制MEK1-ERK2信号转导通路的激活,使其产生精神分裂样症状,这可能也是精神分裂症的发病机制之一。

Study on the Schizoid Symptoms of the Mice Induced by Ketamine and Its Mechanism

Objective To observe the schizoid symptoms of mice induced by ketamine,the changes of CK and NO in serum, and the influences to expression of MEK1 and ERK2 mRNA in frontal lobe. Methods Forty Kunming mice were divided into 4 groups randomly the control group of physiological saline, ketamine groups including small dose group, medium dose group and large dose group, all mice were administrated by intraperitoneal injection and the changes of their behavior were observed after 7 days, CK and NO in serum were
determined by ultraviolet spectrophotometer technique, the expression of MEK1 and ERK2mRNA in frontal lobe,were observed by RT-PCR technique. Results Compared to the control group,obvious changes were observed in mice＇s behavior in every ketamine group,especially in the medium dose group and the large dose group （P〈0.01）. The activity of CK in serum was increased in every ketamine group, and significant difference in large dose group （P〈0.01）, the content of NO in serum was increased significantly （P〈0.01）. In frontal lobe, the expression of MEK1 mRNA was decreased obviously in ketamine me-dium dose group and large dose group,the expression of ERK2 mRNA was decreased obviously in ketamine large dose group（P〈0.05 or 〈0.01）. Conclusion Ketamine increase the activity of CK and content of NO in serum, inhibited the activation of MEK1- ERK2 signaling transduction pathway, and then induce the schizoid symptoms of themice,that may be a pathogenesy of schizophrenia.