抑制胆碱酯酶对精神分裂症动物模型大鼠的记忆力和游离氨基酸的影响

Effects of inhibitive cholinesterase on memory and free amino acid in model rats of schizophrenia

目的:探讨在精神分裂症动物模型大鼠中,动物模型的记忆力和脑组织游离氨基酸与乙酰胆碱含量的变化关系。方法:实验在兰州军区精神病防治中心完成。将8周龄的Wistar雄性大鼠随机分成对照组、模型对照组和治疗组,每组8只。其中对照组空白对照,模型对照组和治疗组用浓度为0.6mg/kg,注射量为5μL/g的5-甲基二氢二苯并环庚稀亚氨马来酸或地卓西平马来酸盐(简称MK801)溶液注射于大鼠左侧腹腔,建立精神分裂症的动物模型;模型对照组以等量生理盐水对照治疗,治疗组以石杉碱甲片进行治疗。采用主动回避反应,一次性被动回避反应,空间分辨记忆3种模式对各组大鼠的学习记忆过程进行系统分析,并测定游离氨基酸水平的变化。结果:3组各8只动物均进入结果分析。①各组大鼠主动回避反应的差异:对照组大鼠主动回避反应习得率明显高于模型对照组和治疗组大鼠,治疗组大鼠主动回避反应习得率明显高于模型对照组大鼠,差异均有显著性意义(P均<0.05);对照组大鼠的主动回避反应消退明显慢于模型对照组和治疗组大鼠,治疗组大鼠的主动回避反应消退明显慢于模型对照组大鼠,差异均有显著性意义(P均<0.05)。②各组大鼠一次性被动回避反应的差异:对照组步入潜伏期最长,治疗组次之,模型对照组最短,且各组间差异有显著性意义(P均<0.05)。③各组大鼠空间分辨记忆的差异:对照组最佳,治疗组次之,模型对照组最差,且各组间差异有显著性意义(P<0.05)。④各组大鼠各脑区游离氨基酸含量的差异:模型对照组大鼠的谷氨酸含量在海马、皮质和纹状体观察区明显低于正常对照组和治疗组,天冬氨酸含量在海马和纹状体观察区低于对照组和治疗组,而氨基丁酸仅在纹状体区高于正常对照组,差异有显著性意义(P均<0.05)。结论:精神分裂症的动物模型伴有学习记忆能力下降,石杉碱甲片能改善精神分裂症动物模型的学习记忆能力,主要是通过抑制乙酰胆碱酯酶的活性同时直接或间接地影响体内氨基酸的含量。

AIM： To explore the relationship of the anamnesis and free amino acids in brain tissue with content of acetylcholine in model rats with schizophrenia. METHODS： The experiment was conducted at the Psychosis Prevention Center of Lanzhou Military Area Command. Wistar male 8-weeks rats were assigned randomly into control group, model control group and treatment group with 8 in each group. The rats in the control group were blank. Those in the model control group and treatment group were injected with MK801 at the concentration of 0.6 mg/kg with 5 μ/g body mass into left abdominal cavity to make animal models of schizophrenia. The rats in the model control group were given same quantity of saline. Those in the treatment group were treated with huperzine A tablet. Process of learning and memory of rats in every group was analyzed systemically with active avoidance reaction （AAR）, once passive avoidance reaction （OPAR）, spatial discrimination memory （SDM）. The level of free amino acids was measured. RESULTS：The rats in the three groups with 8 in each group were all involved in the result analysis. ① Difference of AAR in rats of every group： Acquisition of AAR in rats of the control group was higher significantly than that in the model control group and treatment group. It was higher remarkably in the treatment group than that in the model control group. The difference was significant （P〈0.05）. Extinction of AAR of rats in the control group was slow significantly than that in the model control group and treatment group. Extinction of AAR of rats in the treatment group was slow obviously than that in the model control group. The difference was significant （P〈0.05）. ② Difference of OPAR in rats of every group：It took most long time of rats in the control group, followed by the treatment group, and it took the shortest time of the model control group,and the difference of every group had significant meaning （P〈0.05）. ③ Difference of SDM in rats of every group： It was optimal in the control group, followed by the treatment group, and that in the model control group was the worse, and the difference of every group had significant meaning （P〈0.05）. ④ Difference of content of free amino acid in brain in rats of every group： The content of aminoglutaric acid in hippoeampus, cortex and corpus striatum of rats in the model control group was lower markedly than that in the control group and treatment group. The content of asparagic acid in hippocampus and corpus striatum was lower than that in the control group and treatment group. While amino butyric acid only in corpus striatum was higher than that in the control group, and the difference had apparent significance （P〈0.05）. CONCLUSION： The ability of learning and memory in animal models with schizophrenia has declined. Huperzine A tablets can improve ability of learning and memory in animal models with schizophrenia by restraining the activity of acetylcholinesterase and directly or indirectly work on amino acids simultaneously.