脑外伤后抑郁状态模型的建立及效果评价

【摘要】目的 探讨建立脑外伤后抑郁状态动物模型，并对此模型的建立和有效性做系统评价。方法 本实验在武汉大学医学院实验中心完成。选用48只雄性Wistar大鼠，随机(随机数字法)分为4组，每组12只。①假手术组：每笼6只饲养，正常饮食饮水；②模型组：以自由落体撞击法制作大鼠左侧额叶脑挫裂伤模型，每笼1只饲养，术后1周加以慢性应激和孤养方法，造成脑外伤后抑郁状态动物模型；③脑外伤组：以自由落体撞击法制作大鼠左侧额叶脑挫裂伤模型，每笼6只饲养，正常饮食饮水；④慢性不可预见性温和应激组：每笼1只饲养，采用慢性应激方法结合孤养法造成大鼠慢性应激抑郁模型。 观察各组大鼠蔗糖水试验，自发改变，用高效液相色谱荧光检测法测定各组大鼠脑内海马、前额叶、下丘脑和纹状体不同部位的多巴胺、5-羟色胺、 去甲肾上腺素单胺类神经递质含量。采用SPSS 13.0统计软件分析结果，资料采用单因素方差分析或成组t检验，以P< 0.05为差异具有统计学意义。结果 造模后即予行为学测试，模型组大鼠蔗糖水饮用量逐渐减少，反映模型组大鼠兴趣和缺乏；旷野试验中模型组大鼠水平及垂直得分减少，反映模型组大鼠活动性减少，兴趣缺乏；模型组大鼠游到终点的时间延长，错误次数增加，反映模型组大鼠的学习和记忆能力下降；模型组大鼠海马、前额叶、下丘脑，和纹状体多巴胺、5-羟色胺、去甲肾上腺素含量下降。结论 在左侧额叶脑挫裂伤模型的基础上给予孤养和慢性不可预见的温和性应激，能建立较理想的脑外伤后抑郁状态动物模型。

【关键词】脑外伤；抑郁；动物模型;单胺类神经递质;形态学

Establishment and evaluation of model of depression after traumatic brain injury CHU Sheng-hua, CHEN Er-tao, FENG Dong-fu, MA Yan-bin, ZHU Zhi-an. Departmet of Neurosurgery, NO.省略

【Abstract】Objective To discuss about the establishment of mental depression model by traumatic brain injury in rats， and to evaluate the validity of this model. Methods The study was carried out in the experiment center of Wuhan University. A total of 48 maleWistar rats were randomized（random number） into four groups (n=12, each): (1) in sham operation group, six rats were fed normally in one cage; (2) in model group, the model of the left frontal lobe contusion was made up by hitting with free-fall method on the left cortex of the rat, and subsequently the each of model rats were separately fed in a cage and put them in a lonely environment with chronic stress one week after traumatic brain injury in order to induce them into models of mental depression; (3) in brain trauma group, the trauma model of the left frontal lobe contusion was set up by the same procedure as in model group, and six rats were fed together in one cage; (4) in CUMS group, each rat was fed normally in one cage in a lonely environment after brain trauma made and chronic mild chaotic stress unpredictable to rats was given to induce mental depression. The consumption of sucrose water and the change of animal behavior were observed and the high performance liquid phase electrochemical with fluorescence detector was used to detect the biogenic monoamine neurotransmitter content (dopamine, serotonin and norepinephrine) in the hippocampus, prefrontal cortex, hypothalamus and striatum area in each group. Experimental data were processed with single factor analysis or t test of variance by Statistical Program for Social Sciences Version 13.0 (SPSS13.0) software. P < 0.05 was considered as statistically significant difference.Results After modeling, the rats of four groups were examined by behavioral tests. It was found that the amount of sugar-water consumption by the rats in the model group and CUMP group decreased, implying the absence of interest in eating and anhedonia of the rats in these groups. In open-field test, the rats in the model group, CUMP group and brain trauma group showed reduction in square crossing and rearing, implying the under-activity and absence of interest in activity. In the water maze test, it was found that the rats in the model group, CUMP group and brain trauma group needed much time to reach the end-point and made many errors, implying the lowering ability to learn and memorize. Levels of dopamine, serotonin and norepinephrine in the hippocampus, prefrontal cortex, hypothalamus and striatum area decreased in these rats with traumatized brain in three groups especially in model group and CUMP group. Conclusions It is a valid method for establishing the mental depression model in rats by traumatic brain injury with separately feeding in the lonely environment and given chronic mild chaotic stress unpredictable to rats on the setting of the left frontal lobe contusion.