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目的探讨双环己酮草酰二腙(cuprizone,CPZ)喂养动物模型作为精神分裂症动物模型的合适剂量和CPZ剂量、海马脱髓鞘改变和行为学改变间的关系。方法使用0.2%、0.3%、0.4%(质量分数)3种剂量CPZ喂养C57BL/6鼠6周,与控制组比较体质量、生存时间和行为学的改变情况,运用免疫组化和光密度比较各组小鼠海马CA1区和DG区内髓鞘改变情况,使用体视学方法研究0.2%CPZ组小鼠海马分区内有髓神经纤维改变情况。结果 0.4%CPZ组小鼠生存时间显著性低于控制组(P<0.01),控制组、0.2%CPZ组和0.3%CPZ组的生存时间无统计学差异(P>0.05)。CPZ喂养组小鼠体质量显著性低于控制组(P<0.05),且剂量越高,体质量丢失越严重。0.2%CPZ组小鼠旷场实验在中央区域的活动显著性增高(P<0.05)。0.2%CPZ组和0.3%CPZ组小鼠海马CA1区MBP染色的平均光密度值显著性低于控制组(P<0.01),0.2%CPZ组小鼠海马DG区MBP染色的平均光密度值显著性低于控制组和0.3%CPZ组(P<0.01)。控制组和0.2%CPZ组海马CA1区和DG区体积无显著性差异(P>0.05)。0.2%CPZ组海马CA1区和DG区内有髓神经纤维长度密度和总长度显著性低于控制组(P<0.05)。结论 0.2%CPZ为用于诱导精神分裂症动物模型的适合CPZ剂量,0.2%CPZ喂养6周可导致小鼠海马CA1和DG区内有髓神经纤维脱髓鞘。
OBJECTIVE: To investigate the relationship between the dosage of CPZ and the dosage of CPZ in animal model of schizophrenia and the changes of CPZ dosage, hippocampal demyelination and behavioral changes. Methods C57BL / 6 mice were fed with CPZ at 0.2%, 0.3% and 0.4% (mass fraction) for 6 weeks. The changes of body weight, survival time and behavior were compared with those of the control group. Immunohistochemistry and optical density The changes of myelin in the hippocampal CA1 and DG regions of the mice were observed. The changes of myelinated nerve fibers in the hippocampus of 0.2% CPZ mice were studied by stereological methods. Results The survival time in 0.4% CPZ group was significantly lower than that in control group (P <0.01). There was no significant difference in survival time between control group, 0.2% CPZ group and 0.3% CPZ group (P> 0.05). The body weight of mice in CPZ group was significantly lower than that in control group (P <0.05), and the higher the dose, the more serious the body mass loss. The open field test in 0.2% CPZ group significantly increased in the central area (P <0.05). The average optical density of MBP staining in hippocampal CA1 area of mice in 0.2% CPZ group and 0.3% CPZ group was significantly lower than that in control group (P <0.01), while the average optical density of MBP staining in hippocampal DG area of 0.2% CPZ group was significantly Sex was lower than the control group and 0.3% CPZ group (P <0.01). There was no significant difference in the volume of hippocampal CA1 and DG between control group and 0.2% CPZ group (P> 0.05). The length density and total length of myelinated nerve fibers in CA1 and DG of hippocampus in 0.2% CPZ group were significantly lower than those in control group (P <0.05). Conclusions 0.2% CPZ is a suitable dose of CPZ for inducing schizophrenia in animal models. 0.2% CPZ feeding for 6 weeks resulted in demyelination of myelinated nerve fibers in hippocampal CA1 and DG regions of mice.