抑郁型动脉粥样硬化大鼠模型的建立与评价

Establishment and evaluation of a rat model of co-occurring atherosclerosis and depression symptomatology

目的探讨建立抑郁型动脉粥样硬化大鼠模型的实验方法并评价模型的有效性。方法给大鼠喂食高脂饲料,利用慢性不可预见性应激造成抑郁表现,观察动物摄食量的变化,用旷场试验测定动物行为,检测血清学生化指标,HE染色观察腹主动脉和肝组织病变情况。结果与正常组相比,模型组大鼠食物消耗量明显减少(P<0.01);旷场实验中垂直得分、水平得分、总得分均明显降低(P<0.01);肝、脾、胸腺的脏器系数明显减少(P<0.01);血清中总胆固醇(TC)、低密度脂蛋白(LDL)、白蛋白(ALB)、球蛋白(GLB)、碱性磷酸酶(ALP)、丙二醛(MDA)含量明显升高(P<0.01),高密度脂蛋白(HDL)含量明显降低(P<0.01),超氧化物歧化酶(SOD)活性降低(P<0.05);主动脉内膜-中膜明显增厚、内膜单核细胞、巨噬细胞浸润与聚集增多,内膜表层可见脂纹脂斑病变。结论高脂饲料饲养叠加慢性不可预见性应激,可造成大鼠兼具动脉粥样硬化和抑郁两方面的症状,与伴有抑郁症的动脉粥样硬化病人的临床表现有较好的相似性,是较理想的动物模型。

Aim To explore the validily and reliability of exper- imental rat model of co-occurring atheroselerosis and depression symllomatology. Methods The rat was fed high-fat diet anti exposed to all unpredictable sequence of stressors. The changes of f.od intake in the animals were determined. The behaviors of rats were obselwed by open-field test anti some biochemical markers in serum were measured. Histological changes in ab- dominal aortas and liver were observed by hematoxylin staining. Results Compared wilh the control group, the model group had some ellariges as follows： the food eonsunlptlon decreased markedly （P 〈0. Ol ）;the vertical scores, horizontal scores and tolal scores in open-field lest decreased markedly （ P 〈 O. O1 ） ; the organ coeMeienis of liver, spleen and thoracic gland reduced signitlcantly（ P 〈 0. 01 ） ; the concentrations of TC, LDL, ALB, （,I,B, AI,P and MDA in serum increased markedly （ P 〈 0. Ol ） , the levels of HI）l, and SO1） decreased markedly （ P 〈 0. 01 ） , and tile aortic intima-media area significantly thiekene（l, mono- cytes and macrophages were found aggregating and infiltrating in the inlimal surface and fatty streaks were obvious. Conclusion This rat model fed with high-lat diet and followed by chronic unpredictable mild stress, is characterized with symptoms of both atheroselerosis and depression, which is similar to clinical manifestation of atherosclerotic patients with depression symp- tom. h is an appropriate model of such disease.