7,8-二羟基黄酮对精神分裂症模型大鼠空间认知及海马突触结构的影响

Effects of 7,8-Dihydroxyflavone on Spatial Cognitive Function and Synaptic Structure in Schizophrenia Rat Model

目的探讨特异性Trk B受体激动剂7,8-二羟基黄酮(7,8-DHF)对精神分裂症模型大鼠空间认知及海马突触结构的影响。方法按随机数字表法将出生后6天SD幼鼠分成正常对照组和模型组。第7~11天,正常对照组皮下注射0.9%氯化钠溶液1 m L·kg^(-1),模型组则皮下注射地佐环平0.1 mg·kg^(-1),每天2次。出生后第60天,模型组大鼠随机分成7,8-DHF组和模型对照组,分别给予7,8-DHF(5 mg·kg^(-1))和二甲亚砜(DMSO)腹腔注射,每天1次,连续14 d。正常对照组大鼠注射等容积DMSO。利用水迷宫实验检测大鼠空间认知能力,高尔基染色检测海马神经元树突棘密度,Western blotting检测海马组织蛋白表达及活性。结果旷场实验结果,正常对照组5 min内总运动距离(12.20±1.62)m,模型对照组为(11.73±1.36)m,7,8-DHF组为(12.94±1.09)m。模型对照组大鼠逃避潜伏期和运动距离均显著大于正常对照组(P<0.05),与模型对照组比较,7,8-DHF组模型大鼠逃避潜伏期和运动距离显著缩短(P<0.05);3组大鼠在训练期间游泳速度差异无统计学意义(均P>0.05)。正常对照组大鼠海马神经元树突棘密度(14.2±2.3)/10μm,模型对照组为(8.0±1.9)/10μm(P<0.05),7,8-DHF组为(13.5±1.7)/10μm(P<0.05);正常对照组GluR1蛋白磷酸化水平为(100.0±5.0),模型对照组为(47.9±10.8)(P<0.05),7,8-DHF组为(97.5±9.3)(P<0.05)。结论 7,8-DHF可有效改善精神分裂症模型大鼠空间认知能力,可能与其上调海马神经元的树突棘密度和GluR1蛋白功能有关。

Objective To investigate the effects of specific TrkB receptor agonist 7,8-dihydroxyflavone （ 7,8-DHF） on spatial cognitive function and synaptic structure in schizophrenia rat model. Methods SD infant rats were divided into normal control group and model group according to the random number table method on the 6th day after birth. During the postnatal day 7 to 11, rats in the normal control group received subcutaneous injection of 0.9% sodium chloride solution （1 mL·kg^-1） twice daily, and the rats in the model group were injected with dizocilpine （0.1 mg·kg^-1）. Beginning on the postnatal day 60, model rats were randomly divided into 7,8-DHF group and model control group, which were given intraperitoneal injection of 7,8-DHF （ 5 mg·kg^-1 ） and DMSO once daily for 14 consecutive days, respectively. The rats of normal control group were given equal volume injections of DMSO. Morris water maze task, Golgi staining and Western blotting were adopted to examine spatial cognitive function, hippocampal dendritic spine density, protein expression and activity, respectively. Results The result in the open field test showed that the total travelled distance within 5 min was （12.20±1.62） m in the normal control group, （11.73±1.36） min the model control group and （12.94±1.09） m in the 7,8-DHF group. The escape latency and travelled distance in the model control group were significantly higher than those in the normal control group （P〈0.05）, and the escape latency and travelled distance in rats of 7,8-DHF group were significantly shortened as compared with those in the model control group （P〈0.05）. There was no significant difference in the swimming speed among the three groups （P〉0.05）. The hippocampal dendritic spine density was （14.2±2.3）/10 μm in the normal control group, （8.0±1.9）/10 μm in the model control group, and （13.5±1.7）/10 μm in the 7,8-DHF group, the differences between the three groups were significant （ all P〈0.05）;the phosphorylation level of GluR1 protein was （100.0±5.0） in the normal control group, （47.9±10.8） in the model control group, and （97.5±9.3） in the 7,8-DHF group, and the differences among the three groups were significant （ all P〈0. 05 ） . Conclusion 7, 8-DHF treatment could improve the spatial cognitive function in rat model of schizophrenia and the mechanisms might be related with the increases of hippocampal dendritic spine density and phosphorylated levels of GluR1.