建立实验性大鼠不稳定粥样斑块模型的可行方法

Establishment of a rat atherosclerosis model with unstable plagues

目的 探索一种建立实验性大鼠不稳定粥样斑块模型的可行方法.方法 40只雄性Wistar大鼠随机分为对照组（C组）、大鼠胸主动脉粥样硬化斑块模型组（A1、A2、A3组）,每组各10只.A1、A2模型组大鼠使用高脂饲料＋维生素D3复合造模,A3组大鼠使用高脂饲料＋维生素D3＋大鼠血管内皮球囊损伤复合造模.A1组大鼠喂食高脂饲料1,A2和A3组大鼠喂食高脂饲料2,C组大鼠喂食普通标准饲料.16周后检测各组大鼠身长、体重及血脂水平,观察胸主动脉病理学变化,流式检测外周血T淋巴细胞的数量.结果 各模型组大鼠血脂总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平明显高于C组.A1组大鼠因造模过程中食欲严重低下,16周末死亡6只,剩余4只生长发育缓慢,A2、A3组大鼠体型肥胖,C组大鼠生长发育正常.主动脉苏木素-伊红（HE）染色显示,A3组大鼠胸主动脉形成了不稳定粥样斑块,A1、A2组大鼠胸主动脉只观察到动脉壁硬化,C组大鼠呈现正常形态的胸主动脉.C组、A1组和A2组大鼠外周血T淋巴细胞百分含量显著低于A3组大鼠, A1、A2组大鼠外周血T淋巴细胞百分含量较C组大鼠轻微升高,但差异无统计学意义.结论 高脂饲料的配方及大鼠动脉内膜的损伤对建立大鼠不稳定粥样斑块模型有着至关重要的影响.利用特殊的高脂配方饲料加上维生素D和球囊损伤血管内膜,可以建立一种可行的实验性大鼠不稳定粥样斑块模型.

Objective To establish a rat atherosclerosis model with unstable plagues. Methods Forty male Wistar rats were randomly divided into four groups： control group （Group C ）, atherosclerosis model group （Group A1, A2, A3）, n=10 each. Rats in Group A1 were fed with high fat diet 1 while rats in Group A2 and Group A3 were fed with high fat diet 2. All these three group of rats were treated with Vitamin D3 together with high fat diet. The aorta intimal of rats in Group A3 was injuried after 7 days of high fat diet feeding. Rats in Group C were fed with a standard diet. After 16 weeks, the plasma lipids, growth and body weight of rats were measured and the pathological changes of rat thoracic aorta were observed. Flow cytometry was used to detect the frequency of T lymphocytes in rat peripheral blood. Results Rat plasma levels of total cholesterol （TC） and low density lipoprotein cholesterol （LDL-C） in Group A1, Group A2 and Group A3 were higher than those in Group C. Because of the decreased appetite, 6 rats in Group AI died and the left 4 rats grew slowly. Rats in Group A2 and Group A3 were in obesity. The growth and development in rats of Group C was normal. Unstable atheroselerotic plaques were observed in the rat thoracic aorta in Group A3. In contrast, only aorta sclerosis was observed in the rat thoracic aorta in Group A1 and Group A2. Moreover, rats in Group C displayed normal thoracic aorta. The frequencies of T cells in rat peripheral blood of Group C, Group A1 and Group A2 were significantly decreased compared to the Group A3. There was no significant difference in the frequencies of T cells in rat peripheral blood among Group C, Group A1 and Group A2. Conclusion The components of high fat diet and the vascular injury played an important role in the establishment of a rat atherosclerosis model with unstable plagues. A rat atherosclerosis model with unstable plagues could be established with a special high fat diet feeding plus VitD3 and vascular injury.