基于慢性缺血应激建立血管性抑郁症动物模型

摘要

Objective To build the ideal animal model for depression. Methods Forty SD rats were divided randomly into 4 groups:①sham-operated group; ②operation group: bilateral common carotid artery ligation ( LBCCA ); ③depression group: chronic unpredictable mild stress ( CUMS) combining with solitary, with no surgery;④model group:LBCCA +CUMS and solitary. We observe animals continuously for 21 days to detect the variation of weight, behavioristics, cerebral blood flow and expression level of matrix metalloproteinases ( MMPs ) , brain-derived neurotrophic factor ( BDNF )/tropomyosin related kinase B ( TrkB ) and MMPs mRNA, BDNF/TrkB mRNA. Results Compared with the sham-operated group, model group rats and depression group rats were significantly decreased (P<0. 05 or P<0. 01) in weight, sucrose consumption, movement distance and the number of rearing in open-field test;the blood flow of rats of operation group and model group were significantly decreased (P<0. 01);the expression level of MMP-2 and MMPs mRNA in model group and operation group were increased markedly ( P<0. 01 ) , the expression level of BDNF/TrkB and BDNF/TrkB mRNA in model group and depression group were decreased significantly (P<0. 01). Conclusion The method of LBCCA superposition CUMS combined with solitary simulate well the core symptoms of depression ( lack of sensation, decline of movement and exploration) and the pathomechanism of unbalance of nerve vascular unit. It’s an ideal model for vascular depression, and it can be used in the study of pharmacological experiment and the mechanism of curative effect.%目的：旨在建立血管性抑郁症( vascular depression, VD)的理想动物模型。方法选用SD大鼠40只,采用数字表法随机分为4组：①手术组：双侧颈总动脉结扎( ligation of bilateral common carotid arteries, LBCCA)；②假手术组：同手术组处理,但不结扎；③抑郁组：慢性不可预见性温和应激( chronic unpredictable mild stress, CUMS)结合孤养,不进行手术；④模型组：LBCCA叠加CUMS,结合孤养。连续观察21 d,观测大鼠体质量变化、行为学改变、脑血流量变化以及大鼠大脑基质金属蛋白酶( matrix metalloproteinases, MMPs)、脑源性神经营养因子( brain-derived neurotrophic factor, BDNF)、酪氨酸激酶受体B ( tropomyosin related kinase B, TrkB)蛋白及其mRNA表达水平的变化。结果与假手术组比较,模型组和抑郁组大鼠体质量、糖水消耗百分率、旷场试验运动距离及站立次数均明显降低(P<0．05或P<0．01),手术组及模型组大鼠脑血流量明显降低(P<0．01),手术组及模型组MMP-2及MMP-2 mRNA表达水平显著增高(P<0．01),抑郁组及模型组海马内BDNF/TrkB及BDNF/TrkB mRNA表达均明显降低(P<0．01或P<0．05)。结论 LBCCA叠加CUMS结合孤养方法较好地模拟了抑郁核心症状快感缺乏、运动和探索能下降的行为特征和神经血管单元( neurovascular unit, NVU)稳态失衡的病理机制,是较为理想的血管性抑郁模型,可用于药理实验及治疗效果机制研究。