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目的建立符合临床、具有易行性与广泛适用性的出血性络风内动证动物模型。方法 Apo E(-/-)基因敲除小鼠高脂饲料喂养并于12周龄行右侧颈总动脉套管术,术后随机分为对照组、应激组、Compound组、应激+Compound组。术后4周后对所有小鼠腹腔注射脂多糖1mg/kg,每周2次,共8周;术后8周应激组、应激+Compound组给予限制性精神刺激,每天4h,共4周;术后10周Compound组、应激+Compound组小鼠腹腔注射Compound 48/80 0.5 mg/kg,隔日1次,共4次。术后12周进行血脂检测和斑块病理形态学检测,计算斑块面积、血管管腔狭窄率,比较斑块内脂质、胶原含量、平滑肌细胞和单核/巨噬细胞含量并计算斑块易损指数。结果各组小鼠血脂水平差异均无统计学意义(P>0.05)。与对照组比较,Coumpound组斑块内出血情况明显升高,应激+Compound组总斑块病理形态情况差异有统计学意义(P<0.05)。各组斑块面积、血管管腔狭窄率及斑块中脂质、平滑肌细胞含量比较差异均无统计学意义(P>0.05),而应激+Compound组和Coumpound组的单核/巨噬细胞含量则较对照组明显升高(P<0.05)。应激+Compound组斑块内胶原含量较其余各组减少,而易损指数较其余各组升高(P<0.05)。结论采用脂多糖+应激+Compound 48/80三种因素联合刺激进行出血性络风内动证小鼠模型构建具有较高的斑块易损性和斑块内出血率,可作为出血性络风内动证动物模型的最佳造模方法。
Objective To establish an animal model of hemorrhagic endogenous wind-induced wind movement that is clinically feasible and has a wide range of applicability. Methods Apo E (- / -) knockout mice were fed with high fat diet and right common carotid artery cannula was performed at 12 weeks. The rats were randomly divided into control group, stress group, Compound group, Compound group. Four weeks after operation, all mice were injected intraperitoneally with lipopolysaccharide 1 mg / kg twice a week for 8 weeks. After 8 weeks, the rats in the stress group and the stress + Compound group were given limited mental stimulation, 4 hours a day for a total of 4 Week; 10 weeks after operation, Compound 48 and 80 mg / kg were injected intraperitoneally in the Compound + and Stress + Compound groups, and every other day for 4 times. At 12 weeks after operation, blood lipid and plaque histopathological examination were performed. Plaque area and stenosis rate of blood vessels were calculated. Lipids, collagen contents, smooth muscle cells and monocyte / macrophage contents were compared and plaque Vulnerability Index. Results There was no significant difference in the level of blood lipid between the three groups (P> 0.05). Compared with the control group, the plaque hemorrhage was significantly increased in the Coumpound group, and there was significant difference in the total plaque pathological morphology between the stress + Compound group (P <0.05). There was no significant difference in plaque area, stenosis rate of vascular lumen and lipid, smooth muscle cell content in plaque (P> 0.05), while the expressions of monocyte / macrophage Content was significantly higher than the control group (P <0.05). Compared with the other groups, the content of collagen in the plaque of the stress + Compound group decreased, while the index of vulnerability increased (P <0.05) compared with the other groups. Conclusion The combination of lipopolysaccharide + stress + Compound 48/80 combined with stimulation of haemorrhagic collaterals in mice model has high plaque vulnerability and plaque hemorrhage, which can be used as hemorrhagic collaterals The best animal model of animal models of modeling methods.